Investigating the effects of antiepileptic drugs on the electrophysiology of vision

The principal aim of this work was to examine the effects of antiepileptic drugs (AEDs) on vision. Vigabatrin acts by increasing GABA at brain inhibitory synapses by irreversibly binding to GABA-transaminase. Remacemide is a novel non-competitive NMDA receptor antagonist and fast sodium channel inhibitor that results in the inhibition of the NMDA receptors located in the neuronal membrane calcium channels increasing glutamate in the brain. Vigabatrin has been shown to cause a specific pattern of visual field loss, as one in three adults taking vigabatrin have shown a bilateral concentric constriction. Remacemide has unknown effects on vision. The majority of studies of the effects of AEDs on vision have not included the paediatric population due to difficulties assessing visual field function using standard perimetry testing. Evidently an alternative test is required to establish and monitor visual field problems associated with AEDs both in children and in adults who cannot comply with perimetry. In order to test paediatric patients exposed to vigabatrin, a field-specific visual evoked potential was developed. Other tests performed on patients taking either vigabatrin or remacemide were electroretinograms, electro-oculograms, multifocal VEPs and perimetry. Comparing these tests to perimetry results from vigabatrin patients the field specific VEP was found to have a high sensitivity and specificity, as did the 30Hz flicker amplitude. The modified VEP was also found to provide useful results in vigabatrin patients. Remacemide did not produce a similar visual field loss to vigabatrin although macular vision was affected. The field specific VEP is a useful method for detecting vigabatrin associated visual field loss that is well tolerated by young children. This technique combined with the ERG under light adapted (30Hz flicker) condition is presently the superior method for detecting vigabatrin-attributed peripheral field defects present in children below the developmental age of 9. The effects of AEDs on vision should be monitored carefully and the use of multifocal stimulation allows for specific areas of the retina and visual pathway to be monitored.

Clinical studies of spatial and temporal aspects of vision: an investigation using psychophysical and electrophysiological techniques

Separate physiological mechanisms which respond to spatial and temporal stimulation have been identified in the visual system. Some pathological conditions may selectively affect these mechanisms, offering a unique opportunity to investigate how psychophysical and electrophysiological tests reflect these visual processes, and thus enhance the use of the tests in clinical diagnosis. Amblyopia and optical blur were studied, representing spatial visual defects of neural and optical origin, respectively. Selective defects of the visual pathways were also studied - optic neuritis which affects the optic nerve, and dementia of the Alzheimer type in which the higher association areas are believed to be affected, but the primary projections spared. Seventy control subjects from 10 to 79 years of age were investigated. This provided material for an additional study of the effect of age on the psychophysical and electrophysiological responses. Spatial processing was measured by visual acuity, the contrast sensitivity function, or spatial modulation transfer function (MTF), and the pattern reversal and pattern onset-offset visual evoked potential (VEP). Temporal, or luminance, processing was measured by the de Lange curve, or temporal MTF, and the flash VEP. The pattern VEP was shown to reflect the integrity of the optic nerve, geniculo striate pathway and primary projections, and was related to high temporal frequency processing. The individual components of the flash VEP differed in their characteristics. The results suggested that the P2 component reflects the function of the higher association areas and is related to low temporal frequency processing, while the Pl component reflects the primary projection areas. The combination of a delayed flash P2 component and a normal latency pattern VEP appears to be specific to dementia of the Alzheimer type and represents an important diagnostic test for this condition.

Myopia control with orthokeratology contact lenses in Spain:a comparison of vision-related quality-of-life measures between orthokeratology contact lenses and single-vision spectacles

Purpose: To compare vision-related quality-of-life measures between children wearing orthokeratology (OK) contact lenses and distance single-vision (SV) spectacles. Methods: Subjects 6 to 12 years of age and with myopia of -0.75 to -4.00 diopters and astigmatism less than or equal to 1.00 diopters were prospectively assigned OK contact lens or SV spectacle correction. A pediatric refractive error profile questionnaire was administered at 12- and 24-month intervals to evaluate children's perceptions in terms of overall vision, near vision, far distance vision, symptoms, appearance, satisfaction, activities, academic performance, handling, and peer perceptions. The mean score of all items was calculated as the overall score. Additionally, parents/guardians were asked to rate their child's mode of visual correction and their intention to continue treatment after study completion. Results: Thirty-one children were fitted with OK contact lenses and 30 with SV spectacles. Children wearing OK contact lenses rated overall vision, far distance vision, symptoms, appearance, satisfaction, activities, academic performance, handling, peer perceptions, and the overall score significantly better than children wearing SV spectacles (all P<0.05). Near vision and handling were, respectively, rated better (P<0.001) and similar (P=0.44) for SV spectacles in comparison to OK contact lenses. No significant differences were found between 12 and 24 months for any of the subjective ratings assessed (all P>0.05). Parents/guardians of children wearing OK contact lenses rated visual correction method and intention to continue treatment higher than parents of children wearing SV spectacles (P=0.01). Conclusion: The results indicate that the significant improvement in vision-related quality of life and acceptability with OK contact lenses is an incentive to engage in its use for the control of myopia in children.

From filters to features:Scale-space analysis of edge and blur coding in human vision

To make vision possible, the visual nervous system must represent the most informative features in the light pattern captured by the eye. Here we use Gaussian scale-space theory to derive a multiscale model for edge analysis and we test it in perceptual experiments. At all scales there are two stages of spatial filtering. An odd-symmetric, Gaussian first derivative filter provides the input to a Gaussian second derivative filter. Crucially, the output at each stage is half-wave rectified before feeding forward to the next. This creates nonlinear channels selectively responsive to one edge polarity while suppressing spurious or "phantom" edges. The two stages have properties analogous to simple and complex cells in the visual cortex. Edges are found as peaks in a scale-space response map that is the output of the second stage. The position and scale of the peak response identify the location and blur of the edge. The model predicts remarkably accurately our results on human perception of edge location and blur for a wide range of luminance profiles, including the surprising finding that blurred edges look sharper when their length is made shorter. The model enhances our understanding of early vision by integrating computational, physiological, and psychophysical approaches. © ARVO.

Mach bands and multiscale models of spatial vision:the role of first, second, and third derivative operators in encoding bars and edges

Ernst Mach observed that light or dark bands could be seen at abrupt changes of luminance gradient in the absence of peaks or troughs in luminance. Many models of feature detection share the idea that bars, lines, and Mach bands are found at peaks and troughs in the output of even-symmetric spatial filters. Our experiments assessed the appearance of Mach bands (position and width) and the probability of seeing them on a novel set of generalized Gaussian edges. Mach band probability was mainly determined by the shape of the luminance profile and increased with the sharpness of its corners, controlled by a single parameter (n). Doubling or halving the size of the images had no significant effect. Variations in contrast (20%-80%) and duration (50-300 ms) had relatively minor effects. These results rule out the idea that Mach bands depend simply on the amplitude of the second derivative, but a multiscale model, based on Gaussian-smoothed first- and second-derivative filtering, can account accurately for the probability and perceived spatial layout of the bands. A key idea is that Mach band visibility depends on the ratio of second- to first-derivative responses at peaks in the second-derivative scale-space map. This ratio is approximately scale-invariant and increases with the sharpness of the corners of the luminance ramp, as observed. The edges of Mach bands pose a surprisingly difficult challenge for models of edge detection, but a nonlinear third-derivative operation is shown to predict the locations of Mach band edges strikingly well. Mach bands thus shed new light on the role of multiscale filtering systems in feature coding. © 2012 ARVO.

Blobs versus bars:psychophysical evidence supports two types of orientation response in human color vision

The classic hypothesis of Livingstone and Hubel (1984, 1987) proposed two types of color pathways in primate visual cortex based on recordings from single cells: a segregated, modularpathway that signals color but provides little information about shape or form and a second pathway that signals color differences and so defines forms without the need to specify their colors. A major problem has been to reconcile this neurophysiological hypothesis with the behavioral data. A wealth of psychophysical studies has demonstrated that color vision has orientation-tuned responses and little impairment on form related tasks, but these have not revealed any direct evidence for nonoriented mechanisms. Here we use a psychophysical method of subthreshold summation across orthogonal orientations for isoluminant red-green gratings in monocular and dichoptic viewing conditions to differentiate between nonoriented and orientation-tuned responses to color contrast. We reveal nonoriented color responses at low spatial frequencies (0.25-0.375 c/deg) under monocular conditions changing to orientation-tuned responses at higher spatial frequencies (1.5 c/deg) and under binocular conditions. We suggest that two distinct pathways coexist in color vision at the behavioral level, revealed at different spatial scales: one is isotropic, monocular, and best equipped for the representation of surface color, and the other is orientation-tuned, binocular, and selective for shape and form. This advances our understanding of the organization of the neural pathways involved in human color vision and provides a strong link between neurophysiological and behavioral data. © 2013 ARVO.

Linear binocular combination of responses to contrast modulation:contrast-weighted summation in first- and second-order vision

Binocular combination for first-order (luminancedefined) stimuli has been widely studied, but we know rather little about this binocular process for spatial modulations of contrast (second-order stimuli). We used phase-matching and amplitude-matching tasks to assess binocular combination of second-order phase and modulation depth simultaneously. With fixed modulation in one eye, we found that binocularly perceived phase was shifted, and perceived amplitude increased almost linearly as modulation depth in the other eye increased. At larger disparities, the phase shift was larger and the amplitude change was smaller. The degree of interocular correlation of the carriers had no influence. These results can be explained by an initial extraction of the contrast envelopes before binocular combination (consistent with the lack of dependence on carrier correlation) followed by a weighted linear summation of second-order modulations in which the weights (gains) for each eye are driven by the first-order carrier contrasts as previously found for first-order binocular combination. Perceived modulation depth fell markedly with increasing phase disparity unlike previous findings that perceived first-order contrast was almost independent of phase disparity. We present a simple revision to a widely used interocular gain-control theory that unifies first- and second-order binocular summation with a single principle-contrast-weighted summation-and we further elaborate the model for first-order combination. Conclusion: Second-order combination is controlled by first-order contrast.

+Psychometric evaluation of the MacDQoL individualised measure of the impact of macular degeneration on quality of life

Background: The MacDQoL is an individualised measure of the impact of macular degeneration (MD) on quality of life (QoL). There is preliminary evidence of its psychometric properties and sensitivity to severity of MD. The aim of this study was to carry out further psychometric evaluation with a larger sample and investigate the measure's sensitivity to MD severity. Methods: Patients with MD (n = 156: 99 women, 57 men, mean age 79 ± 13 years), recruited from eye clinics (one NHS, one private) completed the MacDQoL by telephone interview and later underwent a clinic vision assessment including near and distance visual acuity (VA), comfortable near VA, contrast sensitivity, colour recognition, recovery from glare and presence or absence of distortion or scotoma in the central 10° of the visual field. Results: The completion rate for the MacDQoL items was 99.8%. Of the 26 items, three were dropped from the measure due to redundancy. A fourth was retained in the questionnaire but excluded when computing the scale score. Principal components analysis and Cronbach's alpha (0.944) supported combining the remaining 22 items in a single scale. Lower MacDQoL scores, indicating more negative impact of MD on QoL, were associated with poorer distance VA (better eye r = -0.431 p < 0.001; worse eye r = -0.350 p < 0.001; binocular vision r = -0.419 p < 0.001) and near VA (better eye r -0.326 p < 0.001; worse eye r = -0.226 p < 0.001; binocular vision r = -0.326 p < 0.001). Poorer MacDQoL scores were associated with poorer contrast sensitivity (better eye r = 0.392 p < 0.001; binocular vision r = 0.423 p < 0.001), poorer colour recognition (r = 0.417 p < 0.001) and poorer comfortable near VA (r = -0.283, p < 0.001). The MacDQoL differentiated between those with and without binocular scotoma (U = 1244 p < 0.001). Conclusion: The MacDQoL 22-item scale has excellent internal consistency reliability and a single-factor structure. The measure is acceptable to respondents and the generic QoL item, MD-specific QoL item and average weighted impact score are related to several measures of vision. The MacDQoL demonstrates that MD has considerable negative impact on many aspects of QoL, particularly independence, leisure activities, dealing with personal affairs and mobility. The measure may be valuable for use in clinical trials and routine clinical care. © 2005 Mitchell et al; licensee BioMed Central Ltd.

Binocular contrast vision at and above threshold

A fundamental problem for any visual system with binocular overlap is the combination of information from the two eyes. Electrophysiology shows that binocular integration of luminance contrast occurs early in visual cortex, but a specific systems architecture has not been established for human vision. Here, we address this by performing binocular summation and monocular, binocular, and dichoptic masking experiments for horizontal 1 cycle per degree test and masking gratings. These data reject three previously published proposals, each of which predict too little binocular summation and insufficient dichoptic facilitation. However, a simple development of one of the rejected models (the twin summation model) and a completely new model (the two-stage model) provide very good fits to the data. Two features common to both models are gently accelerating (almost linear) contrast transduction prior to binocular summation and suppressive ocular interactions that contribute to contrast gain control. With all model parameters fixed, both models correctly predict (1) systematic variation in psychometric slopes, (2) dichoptic contrast matching, and (3) high levels of binocular summation for various levels of binocular pedestal contrast. A review of evidence from elsewhere leads us to favor the two-stage model. © 2006 ARVO.

On the decline of 1st and 2nd order sensitivity with eccentricity

We studied the relationship between the decline in sensitivity that occurs with eccentricity for stimuli of different spatial scale defined by either luminance (LM) or contrast (CM) modulation. We show that the detectability of CM stimuli declines with eccentricity in a spatial frequency-dependent manner, and that the rate of sensitivity decline for CM stimuli is roughly that expected from their 1st order carriers, except, possibly, at finer scales. Using an equivalent noise paradigm, we investigated the possible reasons for why the foveal sensitivity for detecting LM and CM stimuli differs as well as the reason why the detectability of 1st order stimuli declines with eccentricity. We show the former can be modeled by an increase in internal noise whereas the latter involves both an increase in internal noise and a loss of efficiency. To encompass both the threshold and suprathreshold transfer properties of peripheral vision, we propose a model in terms of the contrast gain of the underlying mechanisms.

Equivalence of physical and perceived speed in binocular rivalry

The relative dominance of gratings engaged in binocular rivalry can be influenced by their surroundings. One striking example occurs when surrounding motion is congruent with one but not the other grating (C. L. Paffen, S. F. te Pas, R. Kanai, M. J. van der Smagt, & F. A. Verstraten, 2004). However, such center-surround stimulus configurations can also modulate perceived speed, via a directionally tuned process (H. P. Norman, J. F. Norman, J. T. Todd, & D. T. Lindsey, 1996). We recorded rivalry for Gabor patches embedded in a drifting noise texture. Gratings whose directions opposed the background motion tended to dominate more, and vice versa, consistent with previous findings. Observers then matched the speed of a drifting noise-embedded Gabor to that of a Gabor surrounded by mean luminance. Surround motion produced substantial changes in perceived speed, by at least a factor of two for all observers. We then asked whether perceived speed could account for the contextual effects on dominance. We measured the effects of speed on rivalry dominance by changing the physical speeds of rivaling gratings, as determined by the matching data. We found the same pattern of dominance as for the context experiment, indicating that perceived and true speed influence rivalry in the same manner. We propose a Bayesian interpretation of the perceived speed illusion.

Visual function and subjective quality of life compared in subjects with acquired macular disease

PURPOSE: To determine the objective measures of visual function that are most relevant to subjective quality of vision and perceived reading ability in patients with acquired macular disease. METHODS: Twenty-eight patients with macular disease underwent a comprehensive assessment of visual function. The patients also completed a vision-related quality-of-life questionnaire that included a section of general questions about perceived visual performance and a section with specific questions on reading. RESULTS: Results of all tests of vision correlated highly with reported vision-related quality-of-life impairment. Low-contrast tests explained most of the variance in self-reported problems with reading. Text-reading speed correlated highly with overall concern about vision. CONCLUSIONS: Reading performance is strongly associated with vision-related quality of life. High-contrast distance acuity is not the only relevant measure of visual function in relation to the perceived visual performance of a patient with macular disease. The results suggest the importance of print contrast, even over print size, in reading performance in patients with acquired macular disease.

Blurred edges look faint, and faint edges look sharp:The effect of a gradient threshold in a multi-scale edge coding model

A multi-scale model of edge coding based on normalized Gaussian derivative filters successfully predicts perceived scale (blur) for a wide variety of edge profiles [Georgeson, M. A., May, K. A., Freeman, T. C. A., & Hesse, G. S. (in press). From filters to features: Scale-space analysis of edge and blur coding in human vision. Journal of Vision]. Our model spatially differentiates the luminance profile, half-wave rectifies the 1st derivative, and then differentiates twice more, to give the 3rd derivative of all regions with a positive gradient. This process is implemented by a set of Gaussian derivative filters with a range of scales. Peaks in the inverted normalized 3rd derivative across space and scale indicate the positions and scales of the edges. The edge contrast can be estimated from the height of the peak. The model provides a veridical estimate of the scale and contrast of edges that have a Gaussian integral profile. Therefore, since scale and contrast are independent stimulus parameters, the model predicts that the perceived value of either of these parameters should be unaffected by changes in the other. This prediction was found to be incorrect: reducing the contrast of an edge made it look sharper, and increasing its scale led to a decrease in the perceived contrast. Our model can account for these effects when the simple half-wave rectifier after the 1st derivative is replaced by a smoothed threshold function described by two parameters. For each subject, one pair of parameters provided a satisfactory fit to the data from all the experiments presented here and in the accompanying paper [May, K. A. & Georgeson, M. A. (2007). Added luminance ramp alters perceived edge blur and contrast: A critical test for derivative-based models of edge coding. Vision Research, 47, 1721-1731]. Thus, when we allow for the visual system's insensitivity to very shallow luminance gradients, our multi-scale model can be extended to edge coding over a wide range of contrasts and blurs. © 2007 Elsevier Ltd. All rights reserved.

Added luminance ramp alters perceived edge blur and contrast:A critical test for derivative-based models of edge coding

In many models of edge analysis in biological vision, the initial stage is a linear 2nd derivative operation. Such models predict that adding a linear luminance ramp to an edge will have no effect on the edge's appearance, since the ramp has no effect on the 2nd derivative. Our experiments did not support this prediction: adding a negative-going ramp to a positive-going edge (or vice-versa) greatly reduced the perceived blur and contrast of the edge. The effects on a fairly sharp edge were accurately predicted by a nonlinear multi-scale model of edge processing [Georgeson, M. A., May, K. A., Freeman, T. C. A., & Hesse, G. S. (in press). From filters to features: Scale-space analysis of edge and blur coding in human vision. Journal of Vision], in which a half-wave rectifier comes after the 1st derivative filter. But we also found that the ramp affected perceived blur more profoundly when the edge blur was large, and this greater effect was not predicted by the existing model. The model's fit to these data was much improved when the simple half-wave rectifier was replaced by a threshold-like transducer [May, K. A. & Georgeson, M. A. (2007). Blurred edges look faint, and faint edges look sharp: The effect of a gradient threshold in a multi-scale edge coding model. Vision Research, 47, 1705-1720.]. This modified model correctly predicted that the interaction between ramp gradient and edge scale would be much larger for blur perception than for contrast perception. In our model, the ramp narrows an internal representation of the gradient profile, leading to a reduction in perceived blur. This in turn reduces perceived contrast because estimated blur plays a role in the model's estimation of contrast. Interestingly, the model predicts that analogous effects should occur when the width of the window containing the edge is made narrower. This has already been confirmed for blur perception; here, we further support the model by showing a similar effect for contrast perception. © 2007 Elsevier Ltd. All rights reserved.