This study compared visual contrast detection with surrogate measures of retinal ganglion cell number (RNFL thickness by OCT) and sampling density (grating resolution acuity) in a group of healthy young adults. To our knowledge, this is the first report to compare the spread of psychometric functions for contrast detection with surrogates of retinal ganglion cell number. We hypothesized that greater numbers of retinal ganglion cells may have the functional consequence of steeper psychometric functions (smaller spread parameter) due to greater signal in response to a stimulus. The data suggest that any associations between contrast detection and clinically measurable estimates of retinal ganglion cell number or sampling density are very weak in this population. Rank correlations between RNFL thickness and contrast-detection threshold and psychometric function slope ranged in magnitude from 0.05 to 0.19 (
Fig. 6). Rank correlations between grating resolution acuity and contrast-detection threshold and psychometric function slope ranged in magnitude from 0.06 to 0.36 when only sampling-limited data were included, and from 0.05 to 0.36 when all data were considered (
Fig. 7). All of these correlations can be considered weak for practical purposes; it is unlikely that any statistical model could be fit that would be useful for predicting contrast-detection threshold or psychometric function slope from either of the surrogate retinal ganglion cell measures.
Although many previous studies have examined the relationship between structural imaging data and visual function in glaucoma, there are limited published data on this relationship in healthy eyes. Garway-Heath et al.
30 reported data from 34 participants aged 58 ± 11 years with normal visual fields, finding no association between temporal neuroretinal rim area and central visual function measured by either perimetry or pattern electroretinogram. Hood and Kardon
31 examined relationships between visual function measured by perimetry in the superior and inferior arcuate areas and corresponding regions of RNFL thickness measured by OCT in 60 participants aged older than 50 years. They found only a weak correlation in both regions (superior arcuate region Pearson's correlation
r = 0.29, inferior region
r = 0.22).
31 Redmond et al.
32 measured both luminance increment detection and grating resolution acuity at 10° eccentricity in superior and inferior visual field (superior, 36° and 144° meridians averaged; inferior, 216° and 324° meridians averaged), and compared both to RNFL thickness measured by OCT in corresponding regions. Their 26 healthy participants were aged 51 to 77 years. The analysis carried out by Redmond et al.
32 primarily compared regression line slopes between healthy and glaucoma groups, and correlation coefficients were reported only for both groups combined. In common with the Hood and Kardon study,
31 the regression line had a positive slope between both functional measures and RNFL thickness in the healthy group alone, but the strength of the association (
R2 or correlation coefficient not reported) can be seen to be weak in their
Figures 2,
3, and
4. Despite differences in participant ages, stimuli, test procedures, and test locations, all of these previous studies provide support for our finding of a very weak, or nonexistent, relationship between contrast-detection thresholds and current structural imaging measures in healthy observers.
The lack of association between contrast-detection thresholds and RNFL thickness in young, healthy participants has implications for the early detection of glaucoma. Glaucoma is often detected when either visual field or RNFL measurements fall outside normative database limits, and the stage of disease at which this happens for various imaging and functional measures has been the topic of considerable debate, as reviewed previously.
14,31,33 The present study shows that the baseline, predisease state of an individual patient could be high in the population distribution with one measure and low in the distribution with the other. With the simplifying assumption of equal progression due to glaucoma in both measures, the measure that started low in the population distribution would fall outside of the normal limits much earlier than the other measure. This implies that both structural and functional measures must be considered for early detection of glaucoma.
There are several reasons why the healthy population variation seen in RNFL thickness measured by OCT may not be an accurate reflection of the healthy population variation in the number of retinal ganglion cells. First, the RNFL contains a non-neural component (blood vessels, glia)
34–36 of variable thickness that remains present in eyes that are blind due to loss of retinal ganglion cells.
37–39 Further variability occurs in retinal ganglion cell axon diameters,
40,41 and the variation in axon density within the RNFL is currently unknown. These sources, in addition to simple measurement variability, will all contribute to the observed population variation in RNFL thickness and weaken any relationship between RNFL thickness and visual function. It is important to note, however, that there also are many more sources of variability in the visual system that could also account for the lack of a relationship with contrast-detection threshold and psychometric function spread. It is possible that any increase in signal due to greater numbers of retinal ganglion cells is countered by an equivalent increase in random noise. Pooling and processing of retinal ganglion cell signals in the lateral geniculate nucleus and visual cortex, as well as additional sources of internal noise in the visual system, are further unknowns in our study that are also likely to vary among individuals, providing further sources of scatter in the relationships.
In this study, we chose to evaluate sectors of RNFL that were related to the visual field regions by a previously published model
27 that has been verified against manual tracing of retinal nerve fiber bundles with good concordance in the tested visual field regions.
42 The model customized these sectors to individuals, although across the range of anatomy in the sample the relevant sectors varied by only a small amount (
Fig. 2). These sectors represent our current best estimate of the anatomical relationship between the tested visual field regions and the RNFL; however, it is worth noting that the sectors relate to larger, arcuate areas of the retina than are sampled by our Gaussian-windowed stimuli. It is possible to use the model to predict narrower regions of RNFL that relate somewhat more closely to the areas of the retina stimulated, but this method would be more vulnerable to small variations in the mapping,
29 and small eye movements during testing. It is not currently possible to isolate RNFL regions relating to visual field areas without also including RNFL regions along the arcuate path between the visual field area and the optic nerve head, and so we are making an assumption that the tested visual field locations are representative of the arcuate areas they sit within. Variation in the spatial distribution and axon size of retinal ganglion cells across the retina will therefore contribute scatter to the measured relationships. Fixation during the psychophysical testing was monitored visually; however, the accuracy of this is limited to approximately 2°, so we cannot rule out a contribution of small eye movements to the scatter found in the relationships reported. Although automated eye tracking would be an improvement to our methods, most of our observers had previous psychophysical experience, and fixation was not seen as problematic during testing.
As a final point, it is worth considering the sample size of 20 observers. In this study, we were specifically interested in whether a clinically meaningful relationship exists between the psychometric function for contrast detection and RNFL thickness. It is plausible that markedly increasing the sample size might render a statistically significant but weak correlation between these measures. However, given the variability in measurements among observers, such a relationship, if present, is unlikely to show any useful predictive power for an individual.
In conclusion, we have measured psychometric functions for contrast detection and compared these with surrogate measures of retinal ganglion cell number and density in a group of healthy young adults. Despite a 2- to 4-fold variation in all measures, we found no correlation between threshold or spread of the contrast-detection psychometric functions and either RNFL thickness or grating resolution acuity that could be exploited for predictive purposes.