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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.

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., (Copyright © 2021. Published by Elsevier Ltd.)

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., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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.

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., (Crown Copyright © 2020. Published by Elsevier Ltd. All rights reserved.)

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 <1s, the other slow with time constant between 40 and 160s. The experiments show that the special case of visual fade involving color represents the sensory basis for many color-related effects involving adaptation.

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 ${\rm L}{:}{\rm M}$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 ${\rm L}{:}{\rm M}$L:M ratio, the paradoxical effect was weak. There was a significant relationship (${{r}^2} = {0.561}$r 2 =0.561) between the balance point and ${\rm L}{:}{\rm M}$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 (FEMA) initiated a program for the re-evaluation of the safety of over 250 natural flavor complexes (NFCs) used as flavor ingredients. This publication, third in the series, considers NFCs composed primarily of constituents with the 3-phenyl-2-propenyl or a cinnamyl functional group, using the procedure outlined in 2005 and updated in 2018 to evaluate the safety of naturally-occurring mixtures for their intended use as flavor ingredients. The procedure relies on a complete chemical characterization of the NFC intended for commerce and organization of each NFC's chemical constituents into well-defined congeneric groups. The safety of the NFC is evaluated using the well-established and conservative threshold of toxicological concern (TTC) concept in addition to data on absorption, metabolism and toxicology of members of the congeneric groups and the NFC under evaluation. Six NFCs from the Myroxylon and Cinnamomum genera, Balsam Oil, Peru (FEMA 2117), Tolu Balsam Extract (FEMA 3069), Cassia Bark Extract (FEMA 2257), Cassia Bark Oil (FEMA 2258), Cinnamon Bark Extract (FEMA 2290) and Cinnamon Bark Oil (FEMA 2291) were evaluated and affirmed as generally recognized as safe (GRAS) under their conditions of intended use as flavor ingredients., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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.

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.

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.

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<0.001]. Post hoc analysis showed that performance was substantially superior under real [chromatic constancy index (cCI)=0.76] compared with simulated cCI=0.55) conditions.

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.

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.

Purpose: 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., Methods: 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., Results: 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., Conclusions: 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., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

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., Competing Interests: Statement on Human Rights Ethical approval All procedures performed in this study were carried out in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent Informed consent was obtained from all individual participants included in the study.

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., (Copyright © 2016 Elsevier Inc. All rights reserved.)

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.

Purpose: 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., Methods: 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., Results: 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., Conclusions: 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.

An overview of electroretinogram response components to incremental and decremental steps in L- and M-cone excitation was obtained in human observers, while varying the spatial properties of the stimulus. Responses to L- and M-cone stimuli of opposite polarity resembled each other, particularly within the central 35° of the retina. All amplitudes grew as stimulus size increased; however, earlier and later components of the On- and Off-responses showed differing degrees of dependency on stimulus size. Thus, they may reflect different proportions of responses originating in parvocellular (less stimulus size-dependent) and magnocellular (more stimulus size-dependent) streams.

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 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.

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., (© 2014 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

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., (© 2015 SAGE Publications.)

Poor vision in low light is a common complaint of elderly people. This poorly understood phenomenon is likely to involve both receptoral and post receptoral mechanisms. We investigated the recovery of contrast thresholds for sine-wave gratings of low spatial frequencies and low mean luminance as a function of time in darkness after photo pigment bleaching. Thirteen subjects aged 30.4 (±10.7) years took part in the study. Contrast thresholds were measured for 15 min following almost complete photo pigment bleaching. The stimuli were achromatic sinusoidal gratings of 0.5, 1 and 2 cycle per degree (cpd) generated on a CRT monitor. They had mean luminance 0.01 cd m(-2) and subtended 10° in diameter. The dynamics of the recovery at each spatial frequency were modelled using monophasic and biphasic exponential decay functions. The data were best modelled by a bi-phasic decay with a distinct transition point around 7 min after the bleach. Both phases followed an exponential decay. The time constant (mean, standard error) for the first phase was 0.35 (0.04) min while for the second phase it was 5.15 (0.27) min. This difference was statistically significant (p < 0.001). A control experiment revealed the second, slower phase was mediated by rod photoreceptors. Maximum contrast sensitivity was reached 15 min after a photic bleach. The dynamics of contrast sensitivity recovery follow two phases and these may be attributed to the cone and rod systems., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Technological advances have led to the development of powerful yet portable tablet computers whose touch-screen resolutions now permit the presentation of targets small enough to test the limits of normal visual acuity. Such devices have become ubiquitous in daily life and are moving into the clinical space. However, in order to produce clinically valid tests, it is important to identify the limits imposed by the screen characteristics, such as resolution, brightness uniformity, contrast linearity and the effect of viewing angle. Previously we have conducted such tests on the iPad 3. Here we extend our investigations to 2 other devices and outline a protocol for calibrating such screens, using standardised methods to measure the gamma function, warm up time, screen uniformity and the effects of viewing angle and screen reflections. We demonstrate that all three devices manifest typical gamma functions for voltage and luminance with warm up times of approximately 15 minutes. However, there were differences in homogeneity and reflectance among the displays. We suggest practical means to optimise quality of display for vision testing including screen calibration.

Cone isolating stimuli were used to assess the temporal frequency response characteristics of L- and M-cone electroretinograms (ERGs) in nine trichromatic and four dichromatic human observers. The stimuli comprised sinusoidal temporal modulations varying from 5 to 100 Hz. ERGs were recorded using corneal fiber electrodes and subjected to fast Fourier transform analysis. At low temporal frequencies (<10  Hz) the L- and M-cone ERGs had similar amplitude and exhibited minimal differences in apparent latency. At higher flicker rates (>20  Hz) L-cone ERGs had greater amplitudes and shorter apparent latencies than the M-cone responses. These differences between the L- and M-cone ERGs are consistent with their mediation by chromatic and luminance postreceptoral processing pathways at low and high temporal frequencies, respectively.

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.

Electroretinograms (ERGs) elicited by transient, square-wave L- and M-cone isolating stimuli were recorded from human trichromatic (n=19) and dichromatic (n=4) observers. The stimuli were generated on a four primary LED stimulator and were equated in terms of cone modulation (cone contrast=0.11) and retinal illuminance (12,000 trolands). L- and M-cone isolated ERGs had waveforms similar to those observed for luminance responses. However, M-cone ERGs exhibited a phase reversal in their responses to onset and offset stimuli relative to the L-cone responses. This on-off response reversal was observed in trichromats but not dichromats. Simultaneous counterphase and inphase combinations of L- and M-cone isolating stimuli generated responses that reflected chromatic and luminance processing, respectively. We conclude that L- and M-cone specific ERGs provide a measure of how photoreceptors contribute to postreceptoral mechanisms.

L- and M-cone driven on- and off- ERG responses and their interactions were examined using full field stimuli with sawtooth temporal profiles. The effects of temporal frequency and contrast were studied. ERG recordings were obtained from 21 trichromatic, 1 protanopic, and 1 deuteranopic subjects. ERGs to L-cone increments and decrements resembled those to M-cone decrements and increments, respectively (i.e., of the opposite polarity). Temporal frequency and contrast had little effect on the implicit times. All response components varied linearly with contrast. When stimulated simultaneously, the responsivities of most components were larger for counterphase than for inphase modulation. The retinal processing leading to an ERG response is reversed for L- and M-cone driven responses.

Purpose: To investigate whether macular pigment optical density (MPOD) is related to dark adaptation in healthy subjects., Methods: 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., Results: 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)., Conclusions: 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.

Background: Macular pigment (MP) might provide some protection against age-related eye disease, and it is now being measured in ophthalmic practice. The purpose of the survey described here was to determine the distribution of MP in a random population of patients in a typical UK ophthalmic practice., Methods: Macular pigment optical density (MPOD) was measured in 56 patients aged 11 to 87 years, mean 52 ± 19, over a 3-month period. Typically, the test requires setting flicker thresholds for a centrally and peripherally viewed blue/green alternating target. Here we describe the results when an age-based estimate of the peripheral value is used, thus avoiding the peripheral setting. In 32 observers, a comparison was made between this and values obtained with the centre and periphery method. Information on smoking habits, iris colour, diabetic status, and ethnicity were recorded., Results: The overall average MPOD for the population obtained with the centre-only approach for 56 individuals was 0.400 ± 0.165. The centre-only technique was an accurate predictor of values based on centre and peripheral measures, with 95% limits of agreement of 0.137 OD units. Pearson's correlation coefficient showed a high correlation between right and left eyes (r = 0.7 (p < 0.001)). There was a small difference between males and females that did not reach statistical significance (r = -0.22). There was a non-statistically significant age-related decline in MPOD in this particular population (r = -0.17). Dark irides were significantly associated with high MPOD (r = 0.28, p < 0.05). MPOD in Type II diabetic patients was 27% lower than that in non-diabetics (r = 0.29, p < 0.05)., Conclusion: The technique provides similar values of MP optical density to previous reports. As with other HFP-based methods, in a small percentage of older patients, more than one measurement is required before satisfactory results are obtained.

Lutein is selectively taken up by the primate retina and plays an important role as a filter for harmful blue light and as an antioxidant. Recent studies have shown that lutein has systemic anti-inflammatory properties. Dietary lutein has been associated with reduced circulating levels of inflammatory biomarkers such as CRP and sICAM. Whether lutein also affects activation of the complement system has not yet been addressed and was the purpose of the study described here. Seventy-two subjects with signs of early macular degeneration were randomly assigned to receive either a 10 mg lutein supplement or a placebo during one year. EDTA blood samples were collected at 0, 4, 8 and 12 months. Complement factor D (CFD), a rate limiting component of the alternative pathway of complement activation and the complement activation products C5a and C3d were determined in the plasma samples by ELISA. A significant 0.11 µg/ml monthly decrease in plasma CFD concentration was observed in the lutein group (p<0.001), resulting in a 51% decrease from 2.3 µg/ml at baseline to 1.0 µg/ml at 12 months. The C5a concentration showed a significant 0.063ng/ml monthly decrease in the lutein group (p<0.001) resulting in a 36% decrease from 2.2ng/ml at baseline to 1.6ng/ml at 12 months. The C3d concentration showed a significant 0.19µg/ml monthly decrease in the lutein group (p=0.004) that gave rise to a 9% decrease from 15.4µg/ml at baseline to 14.4µg/ml at 12 months. In the placebo group we found a significant 0.04 µg/ml monthly decrease in plasma CFD concentration, whereas no changes were observed for C5a and C3d. Lutein supplementation markedly decreases circulating levels of the complement factors CFD, C5a and C3d levels, which might allow a simple method to control this inflammatory pathway of the innate immune system.

Purpose: To characterize the rate of rod-mediated sensitivity decline with age using a PC-driven cathode ray tube (CRT) monitor. To provide data regarding the repeatability of the technique., Methods: Dark adaptation was monitored for 30 min following a minimum 30 % pigment bleach, using a white 1° stimulus (modulated at 1 Hz), presented 11° below fixation on a CRT monitor. Thirty-three subjects with no ocular pathology and normal fundus photographs were divided into two groups: older (≥45, n = 16) and younger (<45, n = 17)., Results: Rod recovery was assessed using component S2 of dark adaptation. S2 was significantly slower in the older (0.19 ± 0.03 log cd.m(-2).min(-1)) compared with the younger group (0.23 ± 0.03 log cd.m(-2).min(-1), t = -4.05, p < 0.0003), despite no difference in visual acuity and fundus appearance. Faster rates of S2 recovery were correlated with lower threshold at 30 min (T30) (r = -0.49). Correlation coefficients between first and second measurements for S2 and T30 were 0.49 (p < 0.009) and 0.84 (p < 0.0001) respectively. The coefficient of repeatability was 0.07 log cd.m(-2).min(-1) for S2 and 0.35 log cd.m(-2) for T30. The coefficients of variation for S2 and T30 were 15 % and 10 % respectively., Conclusions: Dark adaptation is slowed in normal ageing. CRT-based dark adaptometry is easily implemented and highly repeatable. The technique described in this article would be useful for documenting visual changes in future clinical trials assessing retinal health in the older eye with and without ocular pathology.

There are a multitude of applications using modern tablet computers for vision testing that are accessible to ophthalmology patients. While these may be of potential future benefit, they are often unsupported by scientific assessment. This report investigates the pertinent physical characteristics behind one of the most common highest specification tablet computers with regard to its capacity for vision testing. We demonstrate through plotting of a gamma curve that it is feasible to produce a precise programmable range of central luminance levels on the device, even with varying background luminance levels. It may not be possible to display very low levels of contrast, but carefully using the gamma curve information allows a reasonable range of contrast sensitivity to be tested. When the screen is first powered on, it may require up to 15 min for the luminance values to stabilize. Finally, luminance of objects varies towards the edge of the screen and when viewed at an angle. However, the resulting effective contrast of objects is less variable. Details of our assessments are important to developers, users and prescribers of tablet clinical vision tests. Without awareness of such findings, these tests may never reach satisfactory levels of clinical validity and reliability.

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.).

The parallel processing of information forms an important organisational principle of the primate visual system. Here we describe experiments which use a novel chromatic–achromatic temporal compound stimulus to simultaneously identify colour and luminance specific signals in the human electroretinogram (ERG). Luminance and chromatic components are separated in the stimulus; the luminance modulation has twice the temporal frequency of the chromatic modulation. ERGs were recorded from four trichromatic and two dichromatic subjects (1 deuteranope and 1 protanope). At isoluminance, the fundamental (first harmonic) response was elicited by the chromatic component in the stimulus. The trichromatic ERGs possessed low-pass temporal tuning characteristics, reflecting the activity of parvocellular post-receptoral mechanisms. There was very little first harmonic response in the dichromats' ERGs. The second harmonic response was elicited by the luminance modulation in the compound stimulus and showed, in all subjects, band-pass temporal tuning characteristic of magnocellular activity. Thus it is possible to concurrently elicit ERG responses from the human retina which reflect processing in both chromatic and luminance pathways. As well as providing a clear demonstration of the parallel nature of chromatic and luminance processing in the human retina, the differences that exist between ERGs from trichromatic and dichromatic subjects point to the existence of interactions between afferent post-receptoral pathways that are in operation from the earliest stages of visual processing.

Typical daylight extends from blue (morning sky) to orangey red (evening sky) and is represented mathematically as the Daylight Locus in color space. In this study, we investigate the impact of this daylight variation on human color vision. Thirty-eight color normal human observers performed an asymmetric color match in the near peripheral visual field. Unique hues were identified using a naming paradigm. The observers' performance for matching was almost perfectly coincident with the Daylight Locus but declined markedly in other regions. Interobserver variability reached a conspicuous minimum adjacent to the Daylight Locus and was maximal in the red and yellowish-green regions. In the naming task, unique blue and yellow were virtually coincident with the Daylight Locus. The results suggest that the mechanisms of color perception mediated by the phylogenetically older (blue-yellow) color pathway have been strongly influenced by the different phases of daylight.

Cone contrast remains constant, when the same object/background is seen under different illuminations-the von Kries rule [Shevell, Vis. Res. 18, 1649 (1978)]. Here we explore this idea using asymmetric color matching. We find that von Kries adaptation holds, regardless of whether chromatic constancy index is low or high. When illumination changes the stimulus luminance (reflectance), lightness constancy is weak and matching is dictated by object/background luminance contrast. When this contrast is masked or disrupted, lightness constancy mechanisms are more prominent. Thus von Kries adaptation is incompatible with lightness constancy, suggesting that cortical mechanisms must underlie color constancy, as expected from neurophysiological studies [Zeki, Nature 284, 412 (1980); Wild, Nature 313, 133 (1985)]., (© 2012 Optical Society of America)

Certain hues undergo shifts in their appearance when they are viewed by the peripheral retina. This has often been shown on a 3-primary color CRT monitor. To investigate the possible role of metamerism, we replicated our peripheral color matching experiments using Munsell paper stimuli viewed under real and simulated daylight (using a 3-primary projection system). Using stimuli of constant value and chroma (7/4), observers adjusted the hue of a 3 deg target presented 18 deg nasally, until it matched a 1 deg target presented 1 deg nasally. The magnitude and pattern of measured hue shifts were similar to those measured using CRT stimuli. We conclude that the perceived hue shifts that have previously been reported in the peripheral retina are independent of the nature of the stimulus and of the illuminant., (© 2012 Optical Society of America)

A characteristic shift in hue and saturation occurs when colored targets are viewed peripherally compared with centrally. Four hues, one in each of the red, blue, green, and yellow regions of color space, remain unchanged when presented in the peripheral field. Apart from green, these peripherally invariant hues correspond almost exactly in color space with the unique hues. We explore this puzzling observation using asymmetric color-matching and color-naming experiments and computing cone contrasts for peripheral and central stimuli. We find that the difference between cone contrasts for the peripheral and central stimuli reaches a maximum at the chromatic axis corresponding to peripherally invariant green. We speculate that the effect is linked to a weakened signal from M-cones and probably associated with a reduced number of M-cones in peripheral retina., (© 2012 Optical Society of America)

There has been much controversy as to whether there are sex-related differences in human color vision. While previous work has concentrated on testing the central visual field, this study compares male versus female color vision in the near peripheral retina. Male (n = 19) and female (n = 19) color normal observers who exhibited no significant differences either in the midpoints or the ranges of their Rayleigh matches were tested with a color matching paradigm. They adjusted hue and saturation of a 3° test spot (18° eccentricity) until it matched a 1° probe (1° eccentricity). Both groups demonstrated measurable shifts in the appearance of the peripheral color stimuli similar to those that have been previously reported. However, females showed substantially less saturation loss than males (p < 0.003) in the green-yellow region of color space. No significant differences were found in other regions of color space. This difference in the perceived saturation of color stimuli was minimally affected either by the inclusion or exclusion in the analysis of potential heterozygous female carriers of deutan color vision deficiencies. We speculate that this advantage of female over male color vision is conferred by M-cone polymorphism.

Background: The aim was to determine the critical eccentricity at which two methods of elaborating peripheral wavefront measurements are significantly different and to characterise horizontal coma in healthy young adults., Methods: Peripheral aberrations were determined for 20 observers for central and eight peripheral gaze positions up to 20° using an IRX-3 aberrometer. In one subject, additional measurements up to 40° were obtained. Two definitions of stretching coefficients were compared. The raw empirical data were compared with theoretical modelling., Results: For both 3.5 mm and 6.0 mm pupils, no significant differences were observed between recalculated and non-recalculated elliptical pupils for both methods (p > 0.05) up to 20° eccentricity. For eccentricities greater than 20° and up to 40°, significant differences between circular and elliptical pupils at some eccentricities were apparent, which corresponded to theoretical models. Wide individual variations in horizontal coma across the peripheral field were observed., Conclusions: The data suggest that for eyes with average levels of aberrations, the elliptical transformation is of no practical importance for eccentricities up to 20°. In some cases the slope of horizontal coma was reversed compared with previous findings in normal eyes., (© 2011 The Authors. Clinical and Experimental Optometry © 2011 Optometrists Association Australia.)

The electroretinographic response to L- and M-cone isolating stimuli was measured at different luminance levels to study the effect of retinal illuminance on amplitude and phase, and how this may influence estimates of L:M ratios in the retina. It was found that the amplitude of L- and M-cone driven responses increases differently with increasing retinal illuminance: L-cone responses increase more quickly than those of M-cones. The L:M ratio does not change strongly with retinal illuminance. The phase of both L- and M-cone driven responses advances with increasing retinal illuminance. There is considerable interindividual variability in the phase difference between the two, but generally M-cone driven responses are phase advanced., (Copyright © Cambridge University Press, 2011)