Rod- versus cone-driven ERGs at different stimulus sizes in normal subjects and retinitis pigmentosa patients.

PURPOSE: To study how rod- and cone-driven responses depend on stimulus size in normal subjects and patients with retinitis pigmentosa (RP), and to show that comparisons between responses to full-field (FF) and smaller stimuli can be useful in diagnosing and monitoring disorders of the peripheral retina without the need for lengthy dark adaptation periods. METHOD: The triple silent substitution technique was used to isolate L-cone-, M-cone- and rod-driven ERGs with 19, 18 and 33% photoreceptor contrasts, respectively, under identical mean luminance conditions. Experiments were conducted on five normal subjects and three RP patients. ERGs on control subjects were recorded at nine different temporal frequencies (between 2 and 60 Hz) for five different stimulus sizes: FF, 70°, 60°, 50° and 40° diameter circular stimuli. Experiments on RP patients involved rod- and L-cone-driven ERG measurements with FF and 40° stimuli at 8 and 48 Hz. Response amplitudes were defined as those of the first harmonic component after Fourier analysis. RESULTS: In normal subjects, rod-driven responses displayed a fundamentally different behavior than cone-driven responses, particularly at low temporal frequencies. At low and intermediate temporal frequencies (≤ 12 Hz), rod-driven signals increased by a factor of about four when measured with smaller stimuli. In contrast, L- and M-cone-driven responses in this frequency region did not change substantially with stimulus size. At high temporal frequencies (≥ 24 Hz), both rod- and cone-driven response amplitudes decreased with decreasing stimulus size. Signals obtained from rod-isolating stimuli under these conditions are likely artefactual. Interestingly, in RP patients, both rod-driven and L-cone-driven ERGs were similar using 40° and FF stimuli. CONCLUSION: The increased responses with smaller stimuli in normal subjects to rod-isolating stimuli indicate that a fundamentally different mechanism drives the ERGs in comparison with the cone-driven responses. We propose that the increased responses are caused by stray light stimulating the peripheral retina, thereby allowing peripheral rod-driven function to be studied using the triple silent substitution technique at photopic luminances. The method is effective in studying impaired peripheral rod- and cone- function in RP patients.

Human S-cone electroretinograms obtained by silent substitution stimulation.

We used triple silent substitution stimuli to characterize human S-cone electroretinograms (ERGs) in normal trichromats. Short-wavelength-cone (S-cone) ERGs were found to have different morphological features and temporal frequency response characteristics compared to ERGs derived from L-cones, M-cones, and rod photoreceptors in normal participants. Furthermore, in two cases of retinal pathology, blue cone monochromatism (BCM) and enhanced S-cone syndrome (ESCS), S-cone ERGs elicited by our stimuli were preserved and enhanced, respectively. The results from both normal and pathological retinae demonstrate that triple silent substitution stimuli can be used to generate ERGs that provide an assay of human S-cone function.

The morphology of human rod ERGs obtained by silent substitution stimulation.

PURPOSE: To record transient ERGs from the light-adapted human retina using silent substitution stimuli which selectively reflect the activity of rod photoreceptors. We aim to describe the morphology of these waveforms and examine how they are affected by the use of less selective stimuli and by retinal pathology. METHODS: Rod-isolating stimuli with square-wave temporal profiles (250/250 ms onset/offset) were presented using a 4 primary LED ganzfeld stimulator. Experiment 1: ERGs were recorded using a rod-isolating stimulus (63 ph Td, rod contrast, C rod = 0.25) from a group (n = 20) of normal trichromatic observers. Experiment 2: Rod ERGs were recorded from a group (n = 5) using a rod-isolating stimulus (C rod = 0.25) which varied in retinal illuminance from 40 to 10,000 ph Td. Experiment 3: ERGs were elicited using 2 kinds of non-isolating stimuli; (1) broadband and (2) rod-isolating stimuli which contained varying degrees of L- and M-cone excitation. Experiment 4: Rod ERGs were recorded from two patient groups with rod monochromacy (n = 3) and CSNB (type 1; n = 2). RESULTS: The rod-isolated ERGs elicited from normal subjects had a waveform with a positive onset component followed by a negative offset. Response amplitude was maximal at retinal illuminances <100 ph Td and was virtually abolished at 400 ph Td. The use of non-selective stimuli altered the ERG waveform eliciting more photopic-like ERG responses. Rod ERGs recorded from rod monochromats had similar features to those recorded from normal trichromats, in contrast to those recorded from participants with CSNB which had an electronegative appearance. CONCLUSIONS: Our results demonstrate that ERGs elicited by silent substitution stimuli can selectively reflect the operation of rod photoreceptors in the normal, light-adapted human retina.

Test illuminant location with respect to the Planckian locus affects chromaticity shifts of real Munsell chips.

The asymmetric sequential color-matching technique was used to determine the shifts in chromaticity of real Munsell chips induced by four test illuminants. The reference illuminant was C. Illuminants green (G) and purple (P) induced shifts orthogonal to the Planckian locus, while illuminants S and A induced shifts along the Planckian locus. Vectors describing the shifts induced by A and S were quantitatively and qualitatively different from those due to G and P. The data suggest that physiological factors, influenced by the proximity of the Planckian locus, affect chromatic constancy under nonsimulated viewing conditions.

Lightness constancy and its link with cone contrast.

The link between chromatic constancy (compensation for hue and saturation shifts) and lightness constancy (compensation for a change in surface reflectance) was tested theoretically by computing cone contrasts and by asymmetric matching experiments. The effect of a thin achromatic line (a frame) around the test sample was tested empirically. When the samples were outlined by the frame, lightness constancy was increased and chromatic constancy reduced (p<0.001). Changes in luminance are more likely to be compensated when the luminance contrast edge around the test stimulus is disturbed as with the addition of an achromatic frame.

L- and M-cone input to 12Hz and 30Hz flicker ERGs across the human retina.

We recorded L- and M-cone isolating ERGs from human subjects using a silent substitution technique at temporal rates of 12 and 30 Hz. These frequencies isolate the activity of cone-opponent and non-opponent post-receptoral mechanisms, respectively. ERGs were obtained using a sequence of stimuli with different spatial configurations comprising; (1) circular stimuli of different sizes which increased in 10° steps up to 70°diameter, or (2) annular stimuli with a 70° outer diameter but with different sized central ablations from 10° up to 60°. L- and M-cone isolating ERGs were obtained from five colour normal subjects using a DTL fibre electrode. Fourier analysis of the ERGs was performed and we measured the amplitude of the first harmonic of the response. For 12 Hz ERGs the L:M cone response amplitude ratio (L:M(ERG)) was close to unity and remained stable irrespective of the spatial configuration of the stimulus. The maintenance of this balanced ratio points to the existence of cone selective input across the human retina for the L-M cone opponent mechanism. For 30 Hz the L:M(ERG) ratio was greater than unity but varied depending upon which region of the retina was being stimulated. This variation we consider to be a consequence of the global response properties of M-cone ERGs rather than representing a real variation in L:M cone ratios across the retina.

Naming versus matching and the stability of unique hues.

It is known that there is a distortion of hue and saturation in the peripheral visual field. In a previous study, when an asymmetric matching paradigm was used, four hues in the blue, red, yellow and green regions of colour space were unchanged and these were referred to as peripherally invariant (Parry et al., J Opt Soc Am A, 23, 2006, 1586). Three of these invariant hues were similar to unique blue, red and yellow. However, for most observers there was a marked difference between unique and invariant green. To investigate this apparent paradox, we have measured unique hues using a range of eccentricities and colourimetric purities. An asymmetric matching and a 4-AFC paradigm were used to establish peripherally invariant and unique hues, respectively. In the asymmetric matching task the observer matched a peripheral spot with a para-foveal spot, for 24 different hues at 18° eccentricity. In the 4-AFC paradigm, 41 hues were presented 20 times at three purities (0.5, 0.75 and 1.0) and three eccentricities (18°, 10° and 1°). The observer had to name the hues as red, blue, green or yellow. Unique hues were found to be constant with eccentricity and purity. The unique green, established with 4-AFC, was found to differ from the invariant green, determined using the matching task. However, red, blue and yellow invariant hues correspond well with unique hues. The data suggest that different mechanisms mediate the matching of green compared with the identification of unique hues. This is similar to the difference between detection and discrimination of spectral stimuli: the detection process is dominated by the cone opponent mechanisms and is most sensitive, whereas more central processes, serving unique hues, influence discrimination.

Macular pigment measurement in clinics: controlling the effect of the ageing media.

We report a series of experiments designed to ensure that Macular Pigment Optical Density (MPOD) measurements obtained with a clinical instrument are not influenced by lens yellowing and ocular media optical density. These effects were determined in six subjects using seven Lee Colour Temperature Correcting filters to simulate changes in the transmittance of the ocular media with age. Calculated simulated age matched the data linking age and optical density reported in the literature, and the MPOD was independent of simulated age. The instrument allows an estimation of MPOD to be made which is based only on a foveal (centre-only) measurement rather than, as is conventional, making a comparison between foveal and peripheral measurements. We assessed the performance of this facility by comparing the centre-only estimate of MPOD with that obtained from both central and peripheral measurements in 5616 eyes. The 95% limits of agreement for the two estimates was 0.13 OD units.

Nasal-temporal differences in cone-opponency in the near peripheral retina.

The purpose of this study is to establish whether nasal-temporal differences in cone photoreceptor distributions are linked to differences in colour matching performance in the two hemi-fields. Perceived shifts in chromaticity were measured using an asymmetric matching paradigm. They were expressed in terms of hue rotations and relative saturation changes and also in terms of activation levels of L-M or S-(L+M) cone-opponent channels. Up to 19 degrees eccentricity there was little difference in chromaticity shifts between nasal and temporal retina for either channel. For matches beyond 19 degrees L-M activation is significantly lower in the nasal field and the S-(L+M) channel was equally activated in both fields. The data are consistent with the asymmetric distribution of L- and M-cones in the nasal and temporal retinae.

L- and M-cone isolating ERGs: LED versus CRT stimulation.

Using double silent substitution, it is possible to generate L-cone and M-cone isolating electroretinograms (ERGs) on a CRT. A major limitation of the technique is that the depth of modulation of cone classes is limited by the restricted luminance of the phosphors and their spectral overlap. To address this problem we have ported the technique to a four-color LED Ganzfeld stimulus (Diagnosis ColorDome). This allows higher retinal illuminances, higher contrasts, and triple silent substitution. With careful control over the retinal area stimulated, we show that the same data can be recorded from both CRT and LED stimuli when luminance, size and cone contrast are kept constant. Importantly, the different temporal profiles of the two devices do not influence the ERG amplitude and phase plots. We present data over a much wider range of luminances (up to about 10,000 trolands) and contrasts with the LED stimulator than previously reported with CRT screens. We conclude that the close resemblance between data obtained with an LED stimulator and with a CRT screen indicate that the differences have a purely physiological origin.

Reaction time measures of adaptation to chromatic contrast.

Simple reaction times (RTs) were measured to brief temporally blurred (total onset 570 ms) Gaussian isoluminant chromatic patches (s.d. 0.5 degrees) whose chromaticities lay along the cardinal chromatic axes (0 degrees, 90 degrees, 180 degrees, and 270 degrees in MBDKL color space). Bipolar adapting stimuli were employed (0 degrees versus 180 degrees or 90 degrees versus 270 degrees). These were larger Gaussian blobs (s.d. 1 degree), modulating sinusoidally between the two hues at 1 Hz. Throughout, the background was illuminant "C" (x = 0.31, y = 0.316, L = 12.5). In a single run, a series of 64 or 32 stimuli were presented without adaptation, followed by 64 or 32 stimuli each of which was preceded by 3 s of adaptation, either along the same or the orthogonal chromatic axis. Finally, 192 or 128 RTs were recorded to measure the time course of recovery from adaptation. Both adapting and test stimuli were presented at fixed supra-threshold contrasts. The effect of adaptation was seen as a lengthening of the RT, which occurred in the first few seconds of the adaptation period. After cessation of adaptation, there was a similarly rapid shortening of RT, although full recovery took 60-90 s. Adaptation gain functions suggested that the S-(L + M) system was less prone to adaptation than L-M.

Almost complete colour constancy achieved with full-field adaptation.

A successive asymmetric colour-matching task was used to study the changes in colour appearance of simulated Munsell samples. Colour shifts were induced with two Planckian illuminants, standard illuminant A (u'=0.256, v'=0.524) and illuminant S (u'=0.174, v'=0.392). Measurements were conducted with a 20 degrees field and a 120 degrees field. Adaptation period varied from 1 to 30s with the smaller field and from 1 to 60s with the larger field. Colour shifts were specified in terms of a modified Brunswik ratio (BR). Higher values of BR were associated with longer adaptation periods but only when the larger background was used. Supplementary experiments showed that the changes in colour appearance were related to a slight shift in the perceived colour of the background. The timing of the colour shifts are modelled in terms of cone opponent responses. High values of BR correspond to almost complete von Kries adaptation in all three cone types.

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.

Macular pigment and risk for age-related macular degeneration in subjects from a Northern European population.

PURPOSE: Age and advanced disease in the fellow eye are the two most important risk factors for age-related macular degeneration (AMD). In this study, the authors investigated the relationship between these variables and the optical density of macular pigment (MP) in a group of subjects from a northern European population. METHODS: The optical density of MP was measured psychophysically in 46 subjects ranging in age from 21 to 81 years with healthy maculae and in 9 healthy eyes known to be at high-risk of AMD because of advanced disease in the fellow eye. Each eye in the latter group was matched with a control eye on the basis of variables believed to be associated with the optical density of MP (iris color, gender, smoking habits, age, and lens density). RESULTS: There was an age-related decline in the optical density of macular pigment among volunteers with no ocular disease (right eye: r(2) = 0.29, P = 0.0006; left eye: r(2) = 0.29, P < 0.0001). Healthy eyes predisposed to AMD had significantly less MP than healthy eyes at no such risk (Wilcoxon's signed rank test: P = 0.015). CONCLUSIONS: The two most important risk factors for AMD are associated with a relative absence of MP. These findings are consistent with the hypothesis that supplemental lutein and zeaxanthin may delay, avert, or modify the course of this disease.

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.

Spatio-temporal tuning of VEPs: effect of mode of stimulation.

The spatial tuning function of the 8 Hz reversal Visual Evoked Potential (VEP) is frequently bimodal. This amplitude 'notch' largely disappears with 16 Hz pattern onset-offset (on-off) stimulation. To investigate the effect of temporal frequency on this phenomenon, we tested seven subjects using a range of rates centred on 8 Hz (reversal) and 16 Hz (on-off). With reversal, a deep notch was present at all temporal frequencies. A much shallower notch was evident with on-off. The on-off and reversal functions differed only in their low spatial frequency branches (below 4.5 c deg-1) where, as temporal frequency decreased, the reversal response was reduced by 50%, whilst the on-off responses doubled in amplitude. Thus, although they behave differently with on-off and reversal, multiple spatial frequency mechanisms are evident with both forms of stimulation.

Visual changes mediated by beer in retrobulbar neuritis--an investigative case report.

A patient with established retrobulbar neuritis and Uhthoff's phenomenon who claimed that his visual acuity improved after drinking beer was assessed by detailed quantitative psychophysical tests. Studies of electrophysiological responses and biochemical levels of blood serum before and after drinking on several occasions were also made. The results of tests of contrast sensitivity, spectral sensitivity, flicker sensitivity, and visually evoked potential confirmed his observation. Some mechanisms for this phenomenon are considered.

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.

Theoretical and practical performance of a concentric bifocal intraocular implant lens.

Some results from a survey of 43 patients who had a monofocal intra-ocular-lens (IOL) in one eye and a concentric bifocal intra-ocular-lens in the fellow eye are reported. Twenty patients with 6/9 or better post-operative visual acuity in both eyes, participated in the main part of the study. Optical transfer functions for the bifocal lens showed that, compared to an optimal single-vision correction, there is a 50% contrast degradation of the distance retinal image across all spatial frequencies above around 3 c/deg. For the patients in the main study, there was a close correspondence between practical measurement of contrast sensitivity and the theoretical predictions of the modulation transfer functions. Measuring contrast sensitivity proved an effective means of assessing misalignment of the bifocal IOLs.