Ian J. Murray

Macular pigment and age related macular degeneration

The yellow coloration of the macula lutea is attributable to the presence of macular pigment in the axons of its photoreceptors.1 In the 1980s several investigators demonstrated that macular pigment consists of the xanthophyll isomers, lutein and zeaxanthin.2 3 Although the role of the macular pigment remains uncertain, several functions have been hypothesised and these include reduction of the effects of light scatter and chromatic aberration on visual performance,4 5 limitation of the damaging photo-oxidative effects of blue light through its absorption,6-8 and protection against the adverse effects of photochemical reactions because of the antioxidant properties of the carotenoids.9 10 Age related macular degeneration (AMD) is the leading cause of visual loss in people over the age of 65 years in the Western world.11 Although the aetiopathogenesis of AMD remains a matter of debate, there is a growing body of evidence to indicate that oxidative damage plays a role.12-14 Consequently, the possibility that the absorption characteristics and antioxidant properties of macular pigment confer protection against AMD has been postulated.10 15 A proved protective effect of macular pigment may be of therapeutic value, as it has recently been reported that human macular pigment can be augmented with dietary modification.16 In this article we review the current literature germane to macular pigment and AMD, and examine the evidence that retinal carotenoids are protective against AMD. The absorption of blue light by the macular pigment was first described in 1866 by Max Schultze who concluded: “Therefore, under an otherwise equal organisation, a retina without a yellow spot would see more blue light than one with such a spot”.17 He believed that absorption of the “most refractable violet” reduced chromatic aberration, but also hypothesised that macular pigment might provide some protection against the hazards …

Neurophysiological interpretation of human visual reaction times: effect of contrast, spatial frequency and luminance

Neurophysiological studies have demonstrated that in primates Magno and Parvo neurons have distinct contrast gain properties. Reaction Times (RTs) can be used to study supra-threshold contrast coding in humans over the same range of stimulus parameters. RTs to achromatic sinusoidal gratings were measured for a range of spatial frequencies (0.49-17.7 c/degree), stimulus luminances (0.005-20 cd/m2) and contrasts (from threshold to 0.5). The stimuli subtended an angle of 7.2 degrees at a viewing distance of 114 cm. RTs exhibit a linear relationship when plotted against the reciprocal of suprathreshold contrast. The slope of these functions reveals how contrast is linked to RT and can, therefore, be referred to as the RT-contrast factor with units of msec x contrast. A general equation is derived which accounts for all stimulus combinations. RT-based contrast functions resemble closely those obtained neurophysiologically for Magno (M) and Parvo (P) cells. Furthermore, the RT equivalent of contrast gain exhibits qualitatively similar gain characteristics to these neurons for a wide range of luminances and spatial frequencies. Our data support the notion that the sensory component of RTs is limited by the properties of pre-cortical neurons.

Lutein supplementation over a one-year period in early AMD might have a mild beneficial effect on visual acuity: the CLEAR study.

PURPOSE We investigated the effect of daily supplementation with lutein (L) capsules on macular pigment optical density (MPOD) and visual acuity (VA) in patients with early age-related macular degeneration (AMD). METHODS A randomized, double-blind, placebo-controlled, two-center investigation of the effects of L supplementation in early AMD was conducted. The duration of the trial was 12 months. The centers were Manchester, United Kingdom and Maastricht, the Netherlands. L capsules (10 mg Ester) or a placebo (P) were taken daily. There were 72 patients (mean age 70.5 ± 8.7) assigned randomly to either L (n = 36) or P (n = 36) groups. MPOD using a flicker-based technique (MPS9000) and best corrected VA (LogMAR) were measured at the beginning and at 4-month intervals over the duration of the 12-month supplementation period. Blood serum samples were collected to monitor compliance. RESULTS At the end of the trial, an overall increase in the mean MPOD level was found for the L group from 0.38 ± 0.19 to 0.53 ± 0.22 optical density (OD) units. According to a mixed design ANOVA, this was statistically significant (P < 0.001). No change in MPOD was found for the P group. There was no significant change in VA in the L group (n = 36). The P group (n = 36) showed a statistically significant deterioration from 0.05 ± 0.13 to 0.09 ± 0.13 (P < 0.05). When comparing the change in VA over the supplementation period, there was a significant difference between the two groups (P < 0.05). To avoid ceiling effects, 2 subgroups of patients with VA worse than 0.06 at baseline were reanalyzed. In the L subgroup (n = 19) a mean improvement in VA from 0.23 ± 0.12 at baseline to 0.16 ± 0.10 at visit 4 was observed (P < 0.05). In the P subgroup (n = 14), there was a small deterioration from 0.18 ± 0.13 to 0.19 ± 0.12 (P = 0.70). The improvement in VA in the L subgroup was compared to the deterioration in VA in the P group and this effect reached statistical significance (P < 0.05). CONCLUSIONS L supplementation increases MPOD levels in early stage AMD patients. According to the VA measurements, the progress of the disease might be slowed in some patients with augmented levels of MP. (ClinicalTrials.gov number NCT01042860.).

Contrast coding and magno/parvo segregation revealed in reaction time studies

Reaction times (RTs) are obtained for a wide range of contrasts of vertical sinusoidal gratings. The data are plotted as a function of the reciprocal of contrast. In some conditions, a single linear function accounts for the data. In others a clear bi-linear function is obtained. The low and high contrast regions of the function are interpreted as representing magno and parvo activity, respectively. RT-based supra-threshold sensitivity functions are obtained for different luminances, stimulus durations and eccentricities and these are compared with conventional threshold-based sensitivities to establish the extent to which RTs and contrast sensitivity are constrained by the same sensory processes.

Macular pigment optical density measurement; a novel compact instrument

A compact device to derive the optical density of human macular pigment (MP) using heterochromatic flicker photometry is described. The validity of the system is assessed by measuring the optical density spectra of MP in 12 healthy subjects and comparing this with well-established previously published values. The mean spectral absorbance characteristics of MP across subjects corresponds well with accepted values. As reported in other studies, our measurements show a wide variation of MP optical densities between individuals. In our technique within-subject variability is low; standard deviations are between 0.025 and 0.15 in most cases. The overall optical density of MP ranged from 0.08 to 0.84 with a mean of 0.496 and standard deviation of 0.257 at 460 nm. The stimulus size was 0.95 degrees. The unique feature of the technique is that it allows free viewing (not Maxwellian View) of the stimulus, it can be conducted easily and quickly and does not need frequent re-calibration.

Amplitude and phase variations of harmonic components in human achromatic and chromatic visual evoked potentials.

Occipital visual evoked potentials (VEPs) were recorded in response to low-contrast, low spatial-frequency chromatic, and achromatic gratings. Fast Fourier Transform (FFT) and time-domain analysis were used to reveal differences in harmonic content and amplitude of chromatic and achromatic response components over a wide range of temporal frequencies. The chromatic ON/OFF VEP is dominated by the fundamental component indicating that onset and offset responses are different. This type of response is typical of neurons with sustained type response characteristics. Conversely, the achromatic onset VEP contains a predominant second harmonic component in addition to the fundamental. This similarity between onset and offset responses suggests that transient mechanisms are responsible for the generation of achromatic components. Frequency analysis of VEPs elicited by phase-reversing stimuli reveals that all of the response energy is concentrated at the second harmonic of the stimulating frequency. The magnitude of the second harmonic component is maximal for achromatic stimuli and undergoes a distinct minimum for isoluminant, chromatic stimuli. This behavior indicates that under the stimulus conditions used, magnocellular neurons with transient characteristics dominate the reversal VEP.

Correspondence between retinal reflectometry and a flicker-based technique in the measurement of macular pigment spatial profiles

A comparison of macular pigment optical density (MPOD) spatial profiles determined by an optical and a psychophysical technique is presented. We measured the right eyes of 19 healthy individuals, using fundus reflectometry at 0, 1, 2, 4, 6, and 8 deg eccentricity; and heterochromatic flicker photometry (HFP) at 0, 0.5, 1, 2, 3, 4, 5, 6, and 7 deg, and a reference point at 8 deg eccentricity. We found a strong correlation between the two techniques. However, the absolute estimates obtained by fundus reflectometry data were higher than by HFP. These differences could partly be explained by the fact that at 8 deg eccentricity the MPOD is not zero, as assumed in HFP. Furthermore, when performing HFP for eccentricities of <1 deg, we had to assume that subjects set flicker thresholds at 0.4 deg horizontal translation when using a 1-deg stimulus. MPOD profiles are very similar for both techniques if, on average, 0.05 DU is added to the HFP data at all eccentricities. An additional correction factor, dependent on the steepness of the MPOD spatial distribution, is required for 0 deg.

Variant and invariant color perception in the near peripheral retina

Perceived shifts in hue that occur with increasing retinal eccentricity were measured by using an asymmetric color matching paradigm for a range of chromatic stimuli. Across nine observers a consistent pattern of hue shift was found; certain hues underwent large perceived shifts in appearance with increasing eccentricity, while for others little or no perceived shift was measured. In separate color naming experiments, red, blue, and yellow unique hues were found to be correlated with those hues that exhibited little or no perceptual shift with retinal eccentricity. Unique green, however, did not exhibit such a strong correlation. Hues that exhibited the largest perceptual shifts in the peripheral retina were found to correlate with intermediate hues that were equally likely to be identified by adjacent color naming mechanisms. However, once again the correlation was found to be weakest for the green mechanism. These data raise the possibility that perceptually unique hues are linked to color signals that represent the most reliable (minimally variant) chromatic information coming from the retina.

Red-green and blue-yellow mechanisms are matched in sensitivity for temporal and spatial modulation

The spatial and temporal properties of human colour vision are examined using isoluminant, red--green and blue--yellow tritanopic gratings. Chromatic sensitivity is found to be low-pass as a function of both spatial and temporal frequency along all the chromatic axes investigated, including the tritanopic confusion lines employed to examine the properties of the S-cone driven mechanism. Comparison of sensitivity to on-off and contrast reversing stimuli indicates that transient mechanisms contribute to the detection of red--green patterns but that the detection of S-cone specific patterns is governed by sustained mechanisms. By compensating for transient contributions to red--green sensitivity, it is shown that sensitivity of chromatic mechanisms dominated by L- and M-cone input are closely matched to those with S-cone input.

Raised visual detection thresholds depend on the level of complexity of cognitive foveal loading

The objective of the study was to measure the interactions between visual thresholds for a simple light (the secondary task) presented peripherally and a simultaneously performed cognitive task (the primary task) presented foveally. The primary task was highly visible but varied according to its cognitive complexity. Interactions between the tasks were determined by measuring detection thresholds for the peripheral task and accuracy of performance of the foveal task. Effects were measured for 5, 10, 20, and 30 deg eccentricity of the peripherally presented light and for three levels of cognitive complexity. Mesopic conditions (0.5 lx) were used. As expected, the concurrent presentation of the foveal cognitive task reduced peripheral sensitivity. Moreover, performance of the foveal task was adversely affected when conducting the peripheral task. Performance on both tasks was reduced as the level of complexity of the cognitive task increased. There were qualitative differences in task interactions between the central 10 deg and at greater eccentricities. Within 10 deg there was a disproportionate effect of eccentricity, previously interpreted as the ‘tunnel-vision’ model of visual field narrowing. Interactions outside 10 deg were less affected by eccentricity. These results are discussed in terms of the known neurophysiological characteristics of the primary visual pathway.