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To study the physiology of the primate visual system, non-invasive electrophysiological techniques are of major importance. Two main techniques are available: the electroretinogram (ERG), a mass potential originating in the retina, and the visual evoked potential (VEP), which reflects activity in the primary visual cortex. In this overview, the history and the state of the art of these techniques are briefly presented as an introduction to the special issue "New Developments in non-invasive visual electrophysiology". The overview and the special issue can be used as the starting point for exciting new developments in the electrophysiology of primate and mammalian vision.

Simple visual reaction times (RTs) are highly sensitive to the presence of transient activity. Transient and sustained visual mechanisms generate different RT versus contrast functions because they have different gains. To identify non-chromatic (transient) activity, we can compare RT versus contrast functions obtained with either fast or slow onset stimuli. To test this, the stimulus adopted was a temporal modulation along the red–green axis, introducing non-chromatic components by varying the red–green ratio. The technique was sensitive to departures from isoluminance for all observers; therefore, we present this method as a way to detect transient contamination in a chromatic stimulus.

PURPOSE To characterize dark adaptation in patients with pseudoxanthoma elasticum, a systemic disease leading to calcification of elastic tissue including the Bruch membrane. METHODS In this prospective case-control study, dark adaptation thresholds were measured using a Goldmann-Weekers dark adaptometer. Additional assessments included best-corrected visual acuity testing, contrast sensitivity, low luminance deficit, and vision-related quality of life. RESULTS Dark adaptation thresholds were significantly higher, and adaptation periods were prolonged in patients with pseudoxanthoma elasticum (n = 35; 33 with 2 ABCC6 mutations) compared with controls (n = 35). The time to adapt 4 log units (20.6 ± 8.6 vs. 8.0 ± 1.3 minutes) and the mean dark adaptation threshold after 15 minutes (3.5 ± 1.1 vs. 1.8 ± 0.2 log units) were significantly different between patients and controls (both P < 0.001). Low luminance deficits (12.3 ± 6.4 vs. 6.1 ± 4.3 ETDRS letters), contrast sensitivity (1.4 ± 0.3 vs. 1.9 ± 0.1), and low luminance-related quality of life (LLQ score: 1,286 ± 355 vs. 2,167 ± 68) were also significantly worse in patients with pseudoxanthoma elasticum (all, P < 0.001). Two patients were treated with high-dose vitamin A which partially reversed impaired dark adaptation. CONCLUSION Patients with pseudoxanthoma elasticum often have impaired dark adaptation. Positive effects of vitamin A supplementation may indicate restricted retinal access of vitamin A through the Bruch membrane as one possible underlying pathogenic factor.

The main aim of the paper is to discuss current knowledge on how Age Related Macular Degeneration (AMD) affects Dark Adaptation (DA). The paper is divided into three parts. Firstly, we outline some of the molecular mechanisms that control DA. Secondly, we review the psychophysical issues and the corresponding analytical techniques. Finally, we characterise the link between slowed DA and the morphological abnormalities in early AMD. Historically, DA has been regarded as too cumbersome for widespread clinical application. Yet the technique is extremely useful; it is widely accepted that the psychophysically obtained slope of the second rod-mediated phase of the dark adaptation function is an accurate assay of photoreceptor pigment regeneration kinetics. Technological developments have prompted new ways of generating the DA curve, but analytical problems remain. A simple potential solution to these, based on the application of a novel fast mathematical algorithm, is presented. This allows the calculation of the parameters of the DA curve in real time. Improving current management of AMD will depend on identifying a satisfactory endpoint for evaluating future therapeutic strategies. This must be implemented before the onset of severe disease. Morphological changes progress too slowly to act as a satisfactory endpoint for new therapies whereas functional changes, such as those seen in DA, may have more potential in this regard. It is important to recognise, however, that the functional changes are not confined to rods and that building a mathematical model of the DA curve enables the separation of rod and cone dysfunction and allows more versatility in terms of the range of disease severity that can be monitored. Examples are presented that show how analysing the DA curve into its constituent components can improve our understanding of the morphological changes in early AMD.

To study the physiology of the primate visual system, non-invasive electrophysiological techniques are of major importance. Two main techniques are available: the electroretinogram (ERG), a mass potential originating in the retina, and the visual evoked potential (VEP), which reflects activity in the primary visual cortex. In this overview, the history and the state of the art of these techniques are briefly presented as an introduction to the special issue “New Developments in non-invasive visual electrophysiology”. The overview and the special issue can be used as the starting point for exciting new developments in the electrophysiology of primate and mammalian vision.

M-cone stimulation induces a pupil constriction to stimulus offset, whereas, with L cones, the pupil responds conventionally with a constriction to onset. To test the possibility that this paradox is linked to the L : M ratio, we measured the strength of the effect by injecting a variable amount of positive or negative luminance contamination on either side of M-cone isolation and identifying a balance point at which the pupil responded equally to onset and offset. Nineteen individuals were recruited. In observers with low L : M ratio, the paradoxical effect was weak. There was a significant relationship ( r 2 = 0.561 ) between the balance point and L : M ratio. The effect is likely to be linked to strong inhibitory signals associated with cone-opponent pathways.

In 2015, the Expert Panel of the Flavor and Extract Manufacturers Association initiated the safety re-evaluation of over 250 natural flavor complexes (NFCs) used as flavor ingredients. This publication, 4th in a series focusing on the safety evaluation of NFCs, presents an evaluation of NFCs rich in hydroxyallylbenzene and hydroxypropenylbenzene constituents using a procedure initially published in 2005 and updated in 2018 that evaluates the safety of naturally occurring mixtures for their intended use as flavoring ingredients. The procedure requires the characterization of the chemical composition for each NFC and subsequent organization of the constituents into defined congeneric groups. The safety of each NFC is evaluated using the conservative threshold of toxicological concern (TTC) approach together with studies on absorption, metabolism and toxicology of the NFC and its constituent congeneric groups. By the application of this procedure, seven NFCs, derived from clove, cinnamon leaf and West Indian bay leaf were affirmed as “generally recognized as safe (GRAS)” under their conditions of intended use as flavor ingredients. An eighth NFC, an oleoresin of West Indian bay leaf, was affirmed based on its estimated intake, which is below the TTC of 0.15 μg/person per day for compounds with structural alerts for genotoxicity.

Profound vision loss occurs after prolonged exposure to an unchanging featureless visual environment. The effect is sometimes called visual fade. Here we investigate this phenomenon in the color domain using two different experiments. In the first experiment we determine the time needed for a colored background to appear achromatic. Four backgrounds were tested. Each represented the observers’ four unique hues. This adaptation time was compared with time to recover after adaptation Hue shifts at the end of the adaptation period were also measured. There were wide individual differences in adaptation times and recovery times. Overall recovery was faster than adaptation (p < 0.02). There were minimal shifts in hue. In the second experiment the changes in saturation (Munsell chroma) and lightness (Munsell value) of the background were monitored at six time intervals during the adapting process. Again asymmetric matching with Munsell samples was used. There were two distinct components to both the adaptation and recovery phases; one fast with time constant

Purpose: The purpose of this paper is to describe the extent to which scotopic and photopic measures of visual function predict color fundus photograph (CFP) and fundus autofluorescence (FAF) changes in early and intermediate nonexudative AMD.Methods: Sixty-nine observers were recruited: 56 AMD patients (mean age, 73 ± 12.98 years) and 13 controls (mean age, 67.77 ± 9.72 years). A nonmydriatic retinal camera was used to obtain stereo fundus photographs and FAF images were recorded with a cSLO Heidelberg Spectralis HRA+OCT. Visual acuity (VA) was measured using an Early Treatment of Diabetic Retinopathy Study chart. Contrast sensitivity (CS) was assessed with a Pelli-Robson chart. Dark adaptation (DA) curves were recorded at 3° eccentricity using a PC-based technique. Analysis of these curves yielded five parameters: cone threshold (CT), cone time constant (CC), cone-rod break (α), slope of the second rod component (S2), and rod-rod break (β).Results: Both cone and rod sensitivity recovery were grossly abnormal in the patients. The rod recovery slope (S2) most accurately predicted the fundus photograph-based grade and the FAF classification (ρ = 0.61 and ρ = 0.60, respectively; both P < 0.0001). CS showed a strong association with FAF (ρ = 0.50, P < 0.0001) and with fundus photograph-based grade (ρ = 0.38, P < 0.002). There was no correlation between VA and either imaging method.Conclusions: Dynamic, rod-based measures most accurately reflect the severity of early AMD. Although less specific to AMD than DA changes, static photopic abnormalities such as CS also correspond with morphologic changes. Assessment of function in early AMD should include dynamic rod- and cone-mediated measurements of sensitivity recovery.

PURPOSE: To report on the utility of a computer tablet-based method for automated testing of visual acuity in children based on the principles of game design. We describe the testing procedure and present repeatability as well as agreement of the score with accepted visual acuity measures.DESIGN: Reliability and validity study.METHODS: Setting: Manchester Royal Eye Hospital Pediatric Ophthalmology Outpatients Department.PATIENT POPULATION: Total of 112 sequentially recruited patients.INTERVENTION: For each patient 1 eye was tested with the Mobile Assessment of Vision by intERactIve Computer for Children (MAVERIC-C) system, consisting of a software application running on a computer tablet, housed in a bespoke viewing chamber. The application elicited touch screen responses using a game design to encourage compliance and automatically acquire visual acuity scores of participating patients. Acuity was then assessed by an examiner with a standard chart-based near ETDRS acuity test before the MAVERIC-C assessment was repeated.MAIN OUTCOME MEASURE: Reliability of MAVERIC-C near visual acuity score and agreement of MAVERIC-C score with near ETDRS chart for visual acuity.RESULTS: Altogether, 106 children (95%) completed the MAVERIC-C system without assistance. The vision scores demonstrated satisfactory reliability, with test-retest VA scores having a mean difference of 0.001 (SD ±0.136) and limits of agreement of 2 SD (LOA) of ±0.267. Comparison with the near EDTRS chart showed agreement with a mean difference of -0.0879 (±0.106) with LOA of ±0.208.CONCLUSIONS: This study demonstrates promising utility for software using a game design to enable automated testing of acuity in children with ophthalmic disease in an objective and accurate manner.

Many eye diseases require on-going assessment for optimal management, creating an ever-increasing burden on patients and hospitals that could potentially be reduced through home vision monitoring. However, there is limited evidence for the utility of current applications and devices for this. To address this, we present a new automated, computer tablet-based method for self-testing near visual acuity (VA) for both high and low contrast targets. We report on its reliability and agreement with gold standard measures. The Mobile Assessment of Vision by intERactIve Computer (MAVERIC) system consists of a calibrated computer tablet housed in a bespoke viewing chamber. Purpose-built software automatically elicits touch-screen responses from subjects to measure their near VA for either low or high contrast acuity. Near high contrast acuity was measured using both the MAVERIC system and a near Landolt C chart in one eye for 81 patients and low contrast acuity using the MAVERIC system and a 25 % contrast near EDTRS chart in one eye of a separate 95 patients. The MAVERIC near acuity was also retested after 20 min to evaluate repeatability. Repeatability of both high and low contrast MAVERIC acuity measures, and their agreement with the chart tests, was assessed using the Bland-Altman comparison method. One hundred and seventy-three patients (96 %) completed the self- testing MAVERIC system without formal assistance. The resulting MAVERIC vision demonstrated good repeatability and good agreement with the gold-standard near chart measures. This study demonstrates the potential utility of the MAVERIC system for patients with ophthalmic disease to self-test their high and low contrast VA. The technique has a high degree of reliability and agreement with gold standard chart based measurements.

Purpose: The recovery of visual sensitivity after a photobleach in early AMD is slowed in rods but cones also may be abnormal. The purpose of this article was to test different stimulus locations to investigate cone function and its relation to rod abnormalities.Methods: Stimuli were presented at two locations, 3.0° and 5.5°, in the inferior visual field. Post photobleach dark adaptation (DA) curves from 50 early-AMD patients were compared with those from 15 healthy controls of similar age. Curves were characterized in terms of four parameters: ct, cone threshold; α, the transition point from cone to rod function; S2, the slope of the second rod-mediated component; and β, the transition from the second to the third rod-mediated component.Results: There were strong location effects for the healthy group and the AMD group. Cone threshold was higher for the outer compared with the inner stimulus (P = 0.001), S2 was steeper for outer compared with inner (P < 0.001), α was shorter for outer (P = 0.004), and β was shorter for outer than inner (P = 0.002). The high variance in the patient data, particularly for α and β, explained the absence of a group*location interaction in the statistics.Conclusions: The data provide a novel perspective on abnormal cone- and rod-sensitivity recovery in early dry AMD. The comparison of pairs of DA curves from different locations highlights the involvement of cones in the underlying pathology of AMD. Dynamic measures of visual function are particularly sensitive to early AMD.

Accurate color judgments rely on a powerful cognitive component. Here we compare the performance of color constancy under real and simulated conditions. Shifts in the u′v′ color plane induced by illuminant A (2750 K) and illuminant S (>20,000 K) were measured using asymmetric color matching. A general linear model was used to predict performance from the following dependent variables: chroma (“4” and “6”), illuminant (“A” and “S”), presentation mode (“Real” and “Monitor”), and hue zone (“blue,” “green,” “yellow,” “red,” and “purple”). There was a strong overall effect [F(7,264)=78.65, p

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 aim of the study was to determine orientation and spatial frequency sensitivity using reaction times (RTs) in an adaptation paradigm. Simple RTs were measured to the onset of a Gabor patch (SD = 1.2 deg, spatial frequency = 4 cycles deg−1). Observers adapted for 10 s to a 4 cycles deg−1 grating presented at a series of orientations (0, 2, 5, 10, 22.5, 45, 90°) or spatial frequencies (±0.5, 1, and 2 octaves). The contrast of the test grating was 4x each participant's unadapted threshold. The effect of adaptation was evaluated by transforming RTs to effective contrast reduction using RT-based contrast response functions. RTs increased by between ∼ 100 ms to 150 ms when the test and adapting gratings were of the same orientation or spatial frequency. The effect became less pronounced as the difference in orientation or spatial frequency increased. The average bandwidths for orientation and spatial frequency were 17.4° and 1.24 octaves, respectively. The method has some advantages over traditional approaches. It reveals a rapid time course of adaptation recovery with a half-life of about 13 s to 23 s. RTs form a rapid and easily implemented technique for assessing the underlying physiological mechanisms that control adaptation at suprathreshold levels of contrast.

Purpose. We introduce a method for determining the impulse response function (IRF) of the electroretinogram (ERG) derived from responses to temporal white noise (TWN) stimuli. Methods. This white noise ERG (wnERG) was recorded in participants with normal trichromatic vision to full field (Ganzfeld stimuli) and 39.3° diameter focal stimuli at mesopic and photopic mean luminances and at different TWN contrasts. The IRF was obtained by cross correlating the TWN stimulus with the wnERG. Results. We show that wnERG recordings are highly repeatable, with good signal-to-noise ratio and do not lead to blink artefacts. The wnERG resembles a flash ERG waveform with an initial negativity (N1) followed by a positivity (P1), with amplitudes that are linearly related to stimulus contrast. These N1 and N1-P1 components showed commonalties in implicit times with the a- and b-waves of flash ERGs. There was a clear transition from rod to cone driven wnERGs at ~1 photopic cd.m-2. We infer that oscillatory potentials found with the flash ERG, but not the wnERG, may reflect retinal non-linearities due to the compression of energy into a short time period during a stimulus flash. Conclusion. The wnERG provides a new approach to study the physiology of the retina using a stimulation method with adaptation and contrast conditions similar to natural scenes to allow for independent variation of stimulus strength and mean luminance, which is not possible with the conventional flash ERG. Translational Relevance. The white noise ERG methodology will be of benefit for clinical studies and animal models in the evaluation of hypotheses related to cellular redundancy to understand the effects of disease on specific visual pathways.

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. 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. 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. 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.

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

To investigate whether macular pigment optical density (MPOD) is related to dark adaptation in healthy subjects.Dark adaptation was measured after a minimum 30 % pigment bleach in 33 subjects (aged 15-68), using a white 1° stimulus presented 11° below fixation on a cathode ray tube monitor. The luminance range of the monitor was extended using neutral density filters. A heterochromatic flicker photometry based instrument (MPS 9000) was used to measure MPOD.The average MPOD for the whole group was 0.37 ± 0.21 optical density units. Subjects with lighter irides had on average 40 % lower MPOD compared to those with darker irides (0.3 ± 0.20 vs 0.5 ± 0.19). Group mean MPOD was weakly associated with second (r = 0.32, p = 0.07) and third rod-mediated recovery rates (r = 0.31, p = 0.08) and with the rod threshold (r = -0.24, p = 0.18) 30 min after the onset of bleach. MPOD was unrelated to cone time constant (r = -0.02, p = 0.91), cone threshold (r = -0.01, p = 0.96), rod-cone break (r = 0.13, p = 0.45) or the rod-rod break (r = 0.11, p = 0.52). The second rod-mediated recovery rate (S2) for the lower 10th percentile of MPOD (n = 4) was 0.18 log cd.m(-2).min(-1) and 0.24 log cd.m(-2).min(-1) for the upper 10th percentile (n = 4). The two groups were significantly different (t = -2.67, p = 0.037).We report a statistically significant difference between subjects falling in the 10th percentile extremes of MPOD and rod-mediated but not cone-mediated sensitivity recovery. Further investigation into the relationship between MPOD and rod function is warranted, particularly extending the work to encompass those with low MPOD and poor night vision.

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 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.) (Invest Ophthalmol Vis Sci. 2013;54:1781-1788) DOI:10.1167/iovs.12-10715

Purpose: To demonstrate that silent substitution stimuli can be used to generate electroretinograms (ERGs) that effectively isolate rod photoreceptor function in humans without the need for dark adaptation, and that this approach constitutes a viable alternative to current clinical standard testing protocols.Methods: Rod-isolating and non-isolating sinusoidal flicker stimuli were generated on a 4 primary light-emitting diode (LED) Ganzfeld stimulator to elicit ERGs from participants with normal and compromised rod function who had not undergone dark-adaptation. Responses were subjected to Fourier analysis, and the amplitude and phase of the fundamental were used to examine temporal frequency and retinal illuminance response characteristics.Results: Electroretinograms elicited by rod-isolating silent substitution stimuli exhibit low-pass temporal frequency response characteristics with an upper response limit of 30 Hz. Responses are optimal between 5 and 8 Hz and between 10 and 100 photopic trolands (Td). There is a significant correlation between the response amplitudes obtained with the silent substitution method and current standard clinical protocols. Analysis of signal-to-noise ratios reveals significant differences between subjects with normal and compromised rod function.Conclusions: Silent substitution provides an effective method for the isolation of human rod photoreceptor function in subjects with normal as well as compromised rod function when stimuli are used within appropriate parameter ranges.Translational Relevance: This method of generating rod-mediated ERGs can be achieved without time-consuming periods of dark adaptation, provides improved isolation of rod- from cone-based activity, and will lead to the development of faster clinical electrophysiologic testing protocols with improved selectivity.

Two paper-based microfluidic techniques, photolithography and wax patterning, were investigated for their potential to improve upon the sensitivity, reproducibility, and versatility of paper spray mass spectrometry. The main limitation of photolithography was the significant signal (approximately three orders of magnitude) above background which was attributed to the chemicals used in the photoresist process. Hydrophobic barriers created via wax patterning were discovered to have approximately 2 orders of magnitude less background signal compared to analogous barriers created using photolithography. A minimum printed wax barrier thickness of approximately 0.3 mm was necessary to consistently retain commonly used paper spray solvents (1 : 1 water : acetonitrile/methanol) and avoid leakage. Constricting capillary flow via wax-printed channels yielded both a significant increase in signal and detection time for detection of model analytes. This signal increase, which was attributed to restricting the radial flow of analyte/solvent on paper (i.e., a concentrating effect), afforded a significant increase in sensitivity (p ≪ 0.05) for the detection of pesticides spiked into residential tap water using a five-point calibration curve. Finally, unique mixing designs using wax patterning can be envisioned to perform on-paper analyte derivatization.

We investigated the brightness (i.e., perceived luminance) of isolated L- and M-cone pulses to seek a perceptual correlate of our previous reports that M-on electroretinograms resemble L-off responses, implying the operation of post-receptoral opponent processing. Using triple silent substitutions, cone increments were generated in a 4-primary ganzfeld, masked by random positive or negative luminance bias. The results show that M-cone increments decrease in brightness, while L-cone increments increase. These differences became smaller as field size reduced; this was not eccentricity or area dependent. We speculate about early retinal input into brightness perception.

The rate of rod sensitivity recovery following a photobleach is a basic measure of the integrity of the outer retina. Rods are selectively impaired in aging and many disorders of the retina, notably Age-Related Macular Degeneration (AMD). It is not known for certain whether the age-related deficit is a pan-retinal effect or if there are localised regions of impaired rod function. To address this important issue a dual arc stimulus was developed that samples sensitivity recovery in two retinal locations.Arc-shaped stimuli were presented on a black CRT screen at two locations, in the inferior visual field. Following a bleach, which was localised to the stimuli, recovery of sensitivity was measured using a modified method of adjustment technique. Neutral density filters were used to extend the luminance range of the CRT. Sensitivity recovery functions were fitted by non-linear regression to a seven-parameter model.Pairs of sensitivity recovery functions were generated from the stimuli. The cone phases of these functions were identical. The slopes of the S2 sections of the curves were steeper for the outer stimuli for both young (p 0.001) and older (p = 0.003) observers. The difference between the two was the same for the two groups. The α point was reached slightly earlier for the young observers and with the outer stimulus but neither of these effects reached statistical significance. The β point occurred earlier for the outer stimuli and this effect was statistically significant only for the older group.The method places minimal demands on observers. The fact that rod sensitivity recovery is slowed in the older normal eye to the same extent in the two locations suggests that this deficit may be uniform across the retina. As there are localised losses in scotopic function in AMD, the technique is ideally suited to distinguishing impaired recovery dynamics due to normal ageing from those caused by disease.

Key points • It has recently been shown that, with careful control over stimulation, the electroretinogram (ERG) can reflect the properties of the post-receptoral parvocellular (P) and magnocellular (M) pathways, which are thought of as the respective substrates for red‐green colour and luminance vision. • Using a novel compound stimulus, which contains red‐green colour information at the fundamental frequency and luminance information at the second harmonic, we were able to simultaneously record colour and luminance ERGs. • Intrichromats,thetemporaltuningcurvesofthesecomponentsreflectedtheknownproperties of the P and M systems, whereas the dichromats showed negligible chromatic response but a normal achromatic response. • Parallel retinal processing that is relevant for vision can be reflected in the ERG.

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.

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.

M-cone onsets appear dimmer than the background and elicit electroretinograms (ERGs) resembling the light offset response. We sought a corresponding anomalous pupillary light reflex (PLR) using a 4-primary ganzfeld as stimulator and pupillometer. Increments and decrements of white light were compared with M- and L-cone onsets and offsets using silent substitution. Luminance bias (LB) could be added to or subtracted from the cone-isolating stimuli. There was a normal PLR to L-cone increments, but the pupil constricted mainly to M-cone decrements. Changing LB produced a neutral point where on and off responses were balanced. The results reflect ERG and psychophysical studies. This observation may be linked to the antagonistic nature of the M-cone input to cone opponent mechanisms.

It is well known that refractive surgery leads to an increase in higher-order aberrations. These can cause problems such as glare, starburst and halos in vision, particularly in low light levels when the pupil is large. The overall wavefront aberration of the eye is typically non-circularly symmetric due to the presence of aberrations such as coma and trefoil. These asymmetries have been shown to induce orientation-selective effects in grating-based contrast sensitivity tests. Classically, contrast sensitivity is assumed to be independent of orientation and is measured at only one orientation. Examining more orientations may give a better indicator of visual performance when abnormal amounts of aberration are present. To examine this, contrast sensitivity through a dilated pupil was determined for four orientations of a 12 cycles deg(-1) sine wave grating in 12 subjects both before and after refractive surgery. Surgery produced orientation-selective changes in contrast sensitivity in most patients (9 out of 12, p0.05). The correlation between contrast sensitivity and higher-order aberrations was found to improve when several orientations were tested compared with data from only one orientation (combined orientations, r(2) = 0.46, p = 0.007; single orientation r(2) = 0.55, p0 .05 to r(2) = 0.09, p0.05). These results indicate that grating orientation is an important factor when investigating the link between visual performance and higher order aberrations.

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.

Colour information is processed by many stages in the visual system. Primate colour vision relies on three photoreceptors, cones, which sample visible light and send signals to the second stage, cone–opponent units. Surprisingly this stage determines not only the threshold detection for chromatic patches, but also matching surface colours under various illuminations. Hue discrimination at detection thresholds reveals contribution of the third stage, colour-opponency, which determines colour categories, or unique hues. These hues remain constant for para-central, peripheral field locations, providing the reference for veridical vision. However, more challenging tasks of colour identification require contributions from higher colour centres (V4–complex, TEO, IT).The aim of this study is to present key experiments illustrating the contributions of the cone opponent stage and unique hues in low-level colour vision, whereas the effect of damage to various stages will be discussed in terms of the distributed representations in the visual system.The experiments showed that the colour apparatus uses signals derived from the entire visual field (i.e. panoramic viewing), perhaps using some form of spatial and temporal integration. This observation is supported by the fact that when a matching paradigm is used to compare peripheral and central colour samples, peripherally invariant hues correspond to unique hues. And, finally, there is a trade-off between sensitivity and selectivity, and it seems likely that neurons form flexible assemblies which can act together to extract either hue, giving fine hue discrimination but poor sensitivity, or extract contrast giving high chromatic sensitivity but having poor hue discrimination.

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 10000 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.

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 degrees), 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.

PURPOSE: To measure losses in contrast sensitivity at different orientations of grating stimuli in refractive surgery patients and show the importance of orientation when higher-order aberrations (HOAs) are altered. SETTING: Manchester Centre for Vision, Manchester Royal Eye Hospital, Manchester, United Kingdom. METHODS: Contrast sensitivity for sine-wave gratings of 12 cycles per degree was measured in 12 patients before and after different types of refractive surgery. Measurements were taken at 4 orientations with small (3.0 mm) and large (dilated) pupils using a binary search procedure. Higher-order aberrations were also measured. RESULTS: Changes in contrast sensitivity at different orientations were seen in patients before and after the surgery. All patients had significantly higher aberrations after surgery. Patients with increased amounts of postoperative HOAs were more likely to exhibit orientation effects. CONCLUSIONS: When contrast sensitivity is tested with gratings, it is advisable to measure more than 1 orientation. This particularly applies when root-mean-square error values are unusually high, such as in refractive surgery patients.

The human visual system exhibits lower contrast thresholds for detecting vertical and horizontal gratings compared with those orientated obliquely. This is known as the oblique effect and has been thought to be due wholly to neural factors. In this study, sensitivity to gratings of different orientation is compared when viewing with small and large pupils. Optical aberrations increase with pupil size. In some subjects, we find a statistically significant change in sensitivity to some orientations for the large pupil condition. This suggests that there is an optical component to orientation selectivity induced by the higher-order aberrations of the eye.

We have studied the changes that occur in human colour perception in the peripheral retina. By modelling the magnitude of activation produced in the L-M and S-(L+M) cone-opponent systems for matched para-foveal and peripheral chromatic stimuli, we have found that variations in perceived appearance are mirrored by a reduction in function of the L-M opponent system. The operation of the S-cone opponent system is affected to a much lesser degree, implying that there is a changing pattern of predominance between the two cone-opponent mechanisms in the peripheral retina. We will explore possible retinal and cortical bases for these changes.

Straipsnyje keliame hipoteze, kad spalvos suvokimo konstantiskumas, kaip procesas, turi dvi sudedamąsias dalis: lokalų ir globalų procesą. Lokalus procesas – tai skirtumas tarp fono ir spalvoto objekto (mūsų tyrimuose – Manselio pavyzdėlio). Sis procesas nuo adaptacijos nepriklauso ir vyksta tik nedideliame regėjimo lauke. Kitas procesas vyksta bėgant laikui, kai kinta suvokiama spalva. Tai fono spalva. Stebėtojas ją įvertina kaip viso regėjimo lauko spalvinį parametrą, todėl pastarasis procesas – globalus. Spalvų suvokimo konstantiskumo eksperimente abu procesus tyrėme asimetriniu stimulų lyginimo metodu. Bandymams naudojome 7 skirtingus plataus spektro apsvietimo saltinius. Dviejose skirtingose bandymų serijose testiniai stimulai – Manselio 7/4 pavyzdėliai, buvo generuojami monitoriaus ekrane. Bandymuose dalyvavo penki tiriamieji. Spalvų suvokimo konstantiskumas buvo įvertinamas Brunsviko santykiu (BR). Gauti rezultatai rodo, kad adaptaciniai pokyciai nevyksta, kai tiriamųjų regos lauke yra „tuscioji aplinka“. Pasalinus „tusciąją aplinką“, spalvų suvokimo konstantiskumas pagerėja, BR tampa artimas 1. Remdamies bandymų rezultatais galime teigti, kad yra du skirtingi spalvos suvokimo procesai. Vienas yra greitas, beveik suoliskas, nulemtas kontrasto, o kitas lėtesnis, adaptacinio pobūdžio, aiskiai pastebimas po 30 s. Spalvos pokytis (adaptacija) dar įvertinamas oponentinių signalų atsakų apskaiciavimu. Pagrindiniai žodžiai: spalvų suvokimo konstantiskumas, kontrastas, adaptacija, Manselio pavyzdėliai. Factors of Colour Perception Constancy: Contrast and Background Adaptation Ausra Daugirdienė, Rytis Stanikūnas, Henrikas Vaitkevicius, Ian J. Murray, Janus J. Kulikowski Summary Colour constancy is the ability of the human visual system to comprehend the constant colour of an object with no regard to changes in the illumination spectrum. Each year witnesses the appearance of new scientific works in various countries. The works touch upon different aspects of the phenomenon. Although scientific research has been conducted for many years, there is no recognised theory explaining the mechanisms that are decisive for colour constancy. The aim of the present work was to establish the influence of contrast, adaptation and background structure upon colour constancy. All experiments were performed with the application of asymmetric matching. Five subjects took part in the experiments. Colour constancy was examined by performing experiments in three cycles. The test illuminants were two Planckian illuminants, standard illuminant A (u’= 0.2559, v’ = 0.5243), illuminant S (u’= 0.1744, v’= 0.3923) and illuminants r (u’/v’ = 0.2618/0.4533), g (u’/v’ = 0.1517/0.4667), v (u’/v’ = 0.2116/0.3766), y (u’/v’ = 0.1939/0.5180. The first set of 7/4 (value – 7/, chroma – /4) of 10 Munsell samples served as test stimuli in the experiments of the second cycle. Being 2° in size, they were generated in the centre of the monitor. The samples were surrounded by a neutral background, sized N7 20° (N meaning the colour being neutral, with the value of 7). Around the neutral background, subject of the experiment saw the non-radiating part of the screen, which we called the „black surround“ (Fig. 1). In the second set of the experiment, the subjects observed the stimuli through a cardboard tube (Fig. 2). Neutral N7 Munsell samples and a set of 7/4 (value – 7/, chroma – /4) of 10 Munsell samples served as test stimuli in the experiments of the third cycle. Colour constancy is quantitively evaluated on the basis of the Brunswik Ratio (BR) (Troost and de Weert, 1991). Higher values of BR were associated with longer adaptation periods, but only when a larger background was used (second cycle of experiments (Fig. 7)). 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 was modelled in terms of coneopponent responses. Our conclusions are: 1. When stimuli are exposed for a short period of time (1 s), partial colour constancy takes place. It does not change (or changes insignificantly) when the stimulus is observed for a longer time (5 and 30 s). Such colour constancy is determined by fast processes which confirm the influence of simultaneous contrast on colour constancy. 2. When the background is small, the influence of adaptation on colour constancy is little, even it the observation time is long (5 or 30 s). 3. When the background fills the entire field of vision, adaptation results in a high colour constancy perception. Key words: colour constancy, contrast, adaptation, Munsell samples.

PURPOSE: The purpose of this study was to investigate the effect of lutein on systemic complement activation in elderly individuals. METHODS: Seventy patients with signs of early age-related macular degeneration (AMD) were included in this study. All subjects were randomly assigned to receive a 10 mg daily dose of lutein or a placebo for a time period of 1 year. EDTA blood was collected before and at various time-points during the study (0, 4, 8 and 12 months). The plasma level of the soluble complement membrane attack complex sC5b-9 was measured by ELISA. RESULTS: We found a significant 1.1 ng/ml monthly decrease in the plasma sC5b-9 concentration in the lutein group (p < 0.001), resulting in a decrease from 60.3 ng/ml at baseline to 46.3 ng/ml at 12 months. For the placebo group, we found a significant 0.6 ng/ml monthly increase in plasma sC5b-9 concentration (p = 0.001), resulting in an increase from 51.6 ng/ml at baseline to 58.4 ng/ml at 12 months. CONCLUSIONS: Lutein supplementation inhibits the systemic activation of the complement system, which provides further functional evidence for the reported beneficial effects of this carotenoid in the management of AMD.

Changes of color perception in the peripheral field are measured using an asymmetric simultaneous matching paradigm. The data confirm previous observations in that saturation changes can be neutralized if the test target is increased in size. However, this compensation does not apply to hue shifts. We show that some hues remain unchanged with eccentricity whereas others exhibit substantial changes. Here the color shifts are plotted in terms of a second-stage cone opponent model. The data suggest that the S-L+M channel is more robust to increasing eccentricity than the L-M channel. Observations are interpreted in terms of the known underlying morphological and physiological differences in these channels.

The light reflected from an object depends both on the object's surface and on the illuminant. Visual systems attempt to resolve this intrinsic ambiguity by comparing the light reflected from the object with respect to the background by computing the difference between the object-background light sampled by three cones. The cone-contrasts for the sample-background stimulus under the test illumination should correspond to the cone-contrasts for samples matched in appearance under the standard background (C). The validity of this cone-contrast rule (Whittle, 2003) and its possible link with stability of perceived colour was studied here using six test illuminants. A successive asymmetric colour-matching task with 40 simulated Munsell samples (value 7, chroma 4) on a neutral background (N7) was used. The subject adjusted the sample under standard illuminant C to match the colour appearance of the test sample under one of the test illuminants. Brunswik Ratio (BR) was used as an index of stability of colour appearance. When computed with respect to the reference illuminant C, the cone contrast rule was violated (particularly for S-cone-contrast). However, if a new reference point based on the perceived colour of the neutral background under the test illumination was used, the cone contrast rule applied. That is, when cone contrasts of the matching samples are computed with respect to this perceived background, they correspond to cone contrasts of the test stimuli. This represents a form of discounting the illuminant for the purpose of determining an object's cone-contrast against the background, which does not vary with background illumination. These cone contrasts, however, do not provide any information about the colour appearance of objects under particular viewing conditions, unless calibrated against a standard by allowing subjects to learn particular colours.

Functional magnetic resonance imaging (fMRI) techniques were used to study haemodynamic and metabolic responses in human visual cortex during varying arterial blood oxygen saturation levels ( Ysat, determined by pulse-oximeter) and stimulation with contrast-reversing checkerboards. The visual-evoked potential amplitude remained constant at lowered Ysat of 0.82 ± 0.03. Similarly, fMRI cerebral blood flow ( CBF) responses were unchanged during reduced Ysat. In contrast, visual cortex volume displaying blood oxygen level-dependent (BOLD) fMRI response decreased as a function of Ysat, but the BOLD signal change of 3.6% ± 1.4% was constant. Oxygen extraction ratio ( OER) during visual activation showed values of 0.26 ± 0.03 for normal Ysat. At lowered Ysat, two OER patterns were observed. Firstly, a reduced OER of 0.14 ± 0.03 in the visual cortex structures showing BOLD in hypoxia was observed. Secondly, signs of much higher OER in other parts of visual cortex were obtained. T2*-weighted magnetic resonance imaging revealed signal increases by 0.8% ± 0.4% with visual activation during lowered Ysat in the visual cortex structures, which showed BOLD of 3.6% in magnitude under normoxia. Because the CBF response in the visual cortex was quantitatively similar during stimulation in normoxia and hypoxia, attenuated T2*-weighted signal increase in parts of visual cortex indicated high OER during visual activation in hypoxia, which was close to that encountered in the resting brain. These spatially localised regions of tissue oxygen extraction and metabolism argue for dissociation between CBF and BOLD fMRI signals in mild hypoxia. The findings point to heterogeneity with regard to oxygen requirement and its coupling to the haemodynamic response in the brain.

Purpose. Driving is essentially a visuomotor task, and there is now compelling evidence that the disproportionate number of road accidents under night driving conditions is linked to changes in visual performance resulting from reduced lighting. The objective of this article is to establish the extent to which vision is either rod- or cone-dominated under night driving conditions. Methods. Visual thresholds are measured under lighting conditions that simulate urban lighting. Dark adaptation curves are obtained under three ambient lighting conditions ranging from low (0.1 cd/m2) to high (5 cd/m 2) mesopic levels of retinal adaptation using circular discs of different sizes (1??, 2??, 3??, and 5??) presented at retinal eccentricities of 0??, 10??, 20??, 30??, and 40??. Results. The dark adaptation curves exhibit the classic inflection point between rod and cone activity for the lower levels of ambient illumination but a simple monophasic function for the high mesopic levels (>0.5 lux). Adaptation rates are four times faster for the higher compared with the lower illumination level and twice as fast for central compared with peripheral presentation. Conclusions. The data suggest that vision is mediated by cone pathways at 5 lux and by rod pathways at 0.5/0.1 lux. This shift does not profoundly affect sensitivity, but because rod pathways are known to be slower than cone pathways, it will certainly affect observers' ability to respond to rapidly changing viewing conditions such as are encountered when driving at night. Copyright ?? 2005 American Academy of Optometry.

Sequential asymmetrical colour matching of forty Munsell samples simulated under illuminant C and one of eight test illuminants was carried out. The subjects matched the appearance of each sample under illuminant C with its appearance under the test illuminant. Samples and background (N7) were presented for 1 s under the test illuminant and were isoluminant with each other. Subjects adjusted hue, chroma, and value under illuminant C. The experiments distinguished two groups of subjects; some observers needed to reduce the luminance of the sample to make a match while others did not. This ‘dimming’ occurred when the matches were close to cardinal axes, especially the tritanopic confusion line. A model of luminance and cone-opponent mechanisms contributing to brightness can account for the dimming effect. Details of analysis in cone-opponent space (L-M, L+M-S, L+M) are presented in the companion paper (Stanikunas et al, 2005 Perception34 this issue).