ISCEV standard pattern reversal VEP development: paediatric reference limits from 649 healthy subjects.

PURPOSE: To establish the extent of agreement for ISCEV standard reference pattern reversal VEPs (prVEPs) acquired at three European centres, to determine any effect of sex, and to establish reference intervals from birth to adolescence. METHODS: PrVEPs were recorded from healthy reference infants and children, aged 2 weeks to 16 years, from three centres using closely matched but non-identical protocols. Amplitudes and peak times were modelled with orthogonal quadratic and sigmoidal curves, respectively, and two-sided limits, 2.5th and 97.5th centiles, estimated using nonlinear quantile Bayesian regression. Data were compared by centre and by sex using median quantile confidence intervals. The 'critical age', i.e. age at which P100 peak time ceased to shorten, was calculated. RESULTS: Data from the three centres were adequately comparable. Sex differences were not clinically meaningful. The pooled data showed rapid drops in P100 peak time which stabilised by 27 and by 34 weeks for large and small check widths, respectively. Post-critical-age reference limits were 87-115 ms and 96-131 ms for large and small check widths, respectively. Amplitudes varied markedly and reference limits for all ages were 5-57 µV and 3.5-56 µV for large and small check widths, respectively. CONCLUSIONS: PrVEP reference data could be combined despite some methodology differences within the tolerances of the ISCEV VEP Standard, supporting the clinical benefit of ISCEV Standards. Comparison with historical data is hampered by lack of minimum reporting guidelines. The reference data presented here could be validated or transformed for use elsewhere.

Artificial intelligence-based screening for amblyopia and its risk factors: comparison with four classic stereovision tests.

Introduction: The development of costs-effective and sensitive screening solutions to prevent amblyopia and identify its risk factors (strabismus, refractive problems or mixed) is a significant priority of pediatric ophthalmology. The main objective of our study was to compare the classification performance of various vision screening tests, including classic, stereoacuity-based tests (Lang II, TNO, Stereo Fly, and Frisby), and non-stereoacuity-based, low-density static, dynamic, and noisy anaglyphic random dot stereograms. We determined whether the combination of non-stereoacuity-based tests integrated in the simplest artificial intelligence (AI) model could be an alternative method for vision screening. Methods: Our study, conducted in Spain and Hungary, is a non-experimental, cross-sectional diagnostic test assessment focused on pediatric eye conditions. Using convenience sampling, we enrolled 423 children aged 3.6-14 years, diagnosed with amblyopia, strabismus, or refractive errors, and compared them to age-matched emmetropic controls. Comprehensive pediatric ophthalmologic examinations ascertained diagnoses. Participants used filter glasses for stereovision tests and red-green goggles for an AI-based test over their prescribed glasses. Sensitivity, specificity, and the area under the ROC curve (AUC) were our metrics, with sensitivity being the primary endpoint. AUCs were analyzed using DeLong's method, and binary classifications (pathologic vs. normal) were evaluated using McNemar's matched pair and Fisher's nonparametric tests. Results: Four non-overlapping groups were studied: (1) amblyopia (n = 46), (2) amblyogenic (n = 55), (3) non-amblyogenic (n = 128), and (4) emmetropic (n = 194), and a fifth group that was a combination of the amblyopia and amblyogenic groups. Based on AUCs, the AI combination of non-stereoacuity-based tests showed significantly better performance 0.908, 95% CI: (0.829-0.958) for detecting amblyopia and its risk factors than most classical tests: Lang II: 0.704, (0.648-0.755), Stereo Fly: 0.780, (0.714-0.837), Frisby: 0.754 (0.688-0.812), p < 0.02, n = 91, DeLong's method). At the optimum ROC point, McNemar's test indicated significantly higher sensitivity in accord with AUCs. Moreover, the AI solution had significantly higher sensitivity than TNO (p = 0.046, N = 134, Fisher's test), as well, while the specificity did not differ. Discussion: The combination of multiple tests utilizing anaglyphic random dot stereograms with varying parameters (density, noise, dynamism) in AI leads to the most advanced and sensitive screening test for identifying amblyopia and amblyogenic conditions compared to all the other tests studied.

Calibration of random dot stereograms and correlograms free of monocular cues.

Dynamic random dot stereograms (DRDSs) and correlograms (DRDCs) are cyclopean stimuli containing binocular depth cues that are ideally, invisible by one eye alone. Thus, they are important tools in assessing stereoscopic function in experimental or ophthalmological diagnostic settings. However, widely used filter-based three-dimensional display technologies often cannot guarantee complete separation of the images intended for the two eyes. Without proper calibration, this may result in unwanted monocular cues in DRDSs and DRDCs, which may bias scientific or diagnostic results. Here, we use a simple mathematical model describing the relationship of digital video values and average luminance and dot contrast in the two eyes. We present an optimization algorithm that provides the set of digital video values that achieve minimal crosstalk at user-defined average luminance and dot contrast for both eyes based on photometric characteristics of a given display. We demonstrated in a psychophysical experiment with color normal participants that this solution is optimal because monocular cues were not detectable at either the calculated or the experimentally measured optima. We also explored the error by which a range of luminance and contrast combinations can be implemented. Although we used a specific monitor and red-green glasses as an example, our method can be easily applied for other filter based three-dimensional systems. This approach is useful for designing psychophysical experiments using cyclopean stimuli for a specific display.

Validation of dynamic random dot stereotests in pediatric vision screening.

PURPOSE: Stereo vision tests are widely used in the clinical practice for screening amblyopia and amblyogenic conditions. According to literature, none of these tests seems to be suitable to be used alone as a simple and reliable tool. There has been a growing interest in developing new types of stereo vision tests, with sufficient sensitivity to detect amblyopia. This new generation of assessment tools should be computer based, and their reliability must be statistically warranted. The present study reports the clinical evaluation of a screening system based on random dot stereograms using a tablet as display. Specifically, a dynamic random dot stereotest with binocularly detectable Snellen-E optotype (DRDSE) was used and compared with the Lang II stereotest. METHODS: A total of 141 children (aged 4-14, mean age 8.9) were examined in a field study at the Department of Ophthalmology, Pécs, Hungary. Inclusion criteria consisted of diagnoses of amblyopia, anisometropia, convergent strabismus, and hyperopia. Children with no ophthalmic pathologies were also enrolled as controls. All subjects went through a regular pediatric ophthalmological examination before proceeding to the DRDSE and Lang II tests. RESULTS: DRDSE and Lang II tests were compared in terms of sensitivity and specificity for different conditions. DRDSE had a 100% sensitivity both for amblyopia (n = 11) and convergent strabismus (n = 21), as well as a 75% sensitivity for hyperopia (n = 36). However, the performance of DRDSE was not statistically significant when screening for anisometropia. On the other hand, Lang II proved to have 81.8% sensitivity for amblyopia, 80.9% for strabismus, and only 52.8% for hyperopia. The specificity of DRDSE was 61.2% for amblyopia, 67.3% for strabismus, and 68.6% for hyperopia, respectively. Conversely, Lang II showed about 10% better specificity, 73.8% for amblyopia, 79.2% for strabismus, and 77.9% for hyperopia. CONCLUSIONS: The DRDSE test has a better sensitivity for the detection of conditions such as amblyopia or convergent strabismus compared with Lang II, although with slightly lower specificity. If the specificity could be further improved by optimization of the stimulus parameters, while keeping the sensitivity high, DRDSE would be a promising stereo vision test for screening of amblyopia.

Correction: Simple reaction times to cyclopean stimuli reveal that the binocular system is tuned to react faster to near than to far objects.

[This corrects the article DOI: 10.1371/journal.pone.0188895.].

Simple reaction times to cyclopean stimuli reveal that the binocular system is tuned to react faster to near than to far objects.

Binocular depth perception is an important mechanism to segregate the visual scene for mapping relevant objects in our environment. Convergent evidence from psychophysical and neurophysiological studies have revealed asymmetries between the processing of near (crossed) and far (uncrossed) binocular disparities. The aim of the present study was to test if near or far objects are processed faster and with higher contrast sensitivity in the visual system. We therefore measured the relationship between binocular disparity and simple reaction time (RT) as well as contrast gain based on the contrast-RT function in young healthy adults. RTs were measured to suddenly appearing cyclopean target stimuli, which were checkerboard patterns encoded by depth in dynamic random dot stereograms (DRDS). The DRDS technique allowed us to selectively study the stereoscopic processing system by eliminating all monocular cues. The results showed that disparity and contrast had significant effects on RTs. RTs as a function of disparity followed a U-shaped tuning curve indicating an optimum at around 15 arc min, where RTs were minimal. Surprisingly, the disparity tuning of RT was much less pronounced for far disparities. At the optimal disparity, we measured advantages of about 80 ms and 30 ms for near disparities at low (10%) and high (90%) contrasts, respectively. High contrast always reduced RTs as well as the disparity dependent differences. Furthermore, RT-based contrast gains were higher for near disparities in the range of disparities where RTs were the shortest. These results show that the sensitivity of the human visual system is biased for near versus far disparities and near stimuli can result in faster motor responses, probably because they bear higher biological relevance.

Maturation of cyclopean visual evoked potential phase in preterm and full-term infants.

PURPOSE: P1 is the major positive component of pattern-reversal visual evoked potentials (PR-VEPs). The rapid decrease of its latency correlates with the progressive myelination in the developing infant brain, which affects signal transmission in the visual system. An age-dependent phase shift, analogous to P1 peak latency, can be observed in dynamic random dot correlogram (DRDC)-evoked VEPs (DRDC-VEPs), a method used to assess binocular function. Our goal was to study the relationship between cyclopean DRDC-VEP phases and PR-VEP P1 latencies in full-term and preterm infants so as to further explore the experience dependence of early binocular developmental processes. METHODS: DRDC-VEPs and PR-VEPs were recorded in 128 full-term and 47 preterm healthy infants and toddlers. DRDC stimuli were presented on the red and green channels of a CRT monitor while infants wore red-green goggles for dichoptic viewing. Reliability of VEP responses was assessed by the statistic. Logistic function was fit to the phase and latency data as a function of age, and goodness of fit was assessed by analysis of residuals. RESULTS: The phase shift of DRDC-VEPs and the rapid decrease of P1 latencies occur at identical postconceptual ages. A correlation also was found between P1 latencies and DRDC-VEP phases. CONCLUSIONS: Although development of binocularity is an extremely experience-dependent process, our data suggest that DRDC-VEP phase and P1 latency mature independently from visual experience. We propose that both the phase shift and decreasing P1 latency are indicators of myelination and increasingly faster signal transmission in the developing visual system.

Effects of luminance on dynamic random-dot correlogram evoked visual potentials.

Although dynamic random-dot correlogram evoked visual potentials (DRDC-VEPs) are a three-decade-old method to detect the cortical binocularity in humans and animals, our knowledge of the influence of fundamental stimulus parameters and the underlying cerebral processing mechanisms has remained limited. The purpose of this study was to evaluate the effect of luminance on DRDC-VEPs in adults. The variability and detectability of DRDC-VEPs were investigated under different stimulus luminance conditions with neutral density filters. Our results have demonstrated that DRDC-VEPs can be evoked in a wide luminance range, and the response amplitude was practically independent of luminance between 4.75 cd m(-2) and 0.015 cd m(-2), while DRDC-VEP latencies showed a strong linear correlation with log luminance. There is, however, a limit (0.06 cd m(-2)) below which DRDC-VEPs are not reliably recordable. Luminance reduction-induced delays in DRDC-VEP latencies cannot be explained simply by retinal mechanisms, since their regression slope does not follow the course of electroretinogram and cortical evoked potential latencies. Luminance independence of DRDC-VEP amplitude suggests that binocular correlation-processing cortical neurons receive input predominantly from the magnocellular visual pathway.

Early-onset binocularity in preterm infants reveals experience-dependent visual development in humans.

Although there is a great deal of knowledge regarding the phylo- and ontogenetic plasticity of the neocortex, the precise nature of environmental impact on the newborn human brain is still one of the most controversial issues of neuroscience. The leading model-system of experience-dependent brain development is binocular vision, also called stereopsis. Here, we show that extra postnatal visual experience in preterm human neonates leads to a change in the developmental timing of binocular vision. The onset age of binocular function, as measured by the visual evoked response to dynamic random dot correlograms (DRDC-VEP), appears to be at around the same time after birth in preterm (4.07 mo) and full-term (3.78 mo) infants. To assess the integrity of the visual pathway in the studied infants, we also measured the latency of the visual-evoked response to pattern reversal stimuli (PR-VEP). PR-VEP latency is not affected by premature birth, demonstrating that the maturation of the visual pathway follows a preprogrammed developmental course. Despite the immaturity of the visual pathway, clearly demonstrated by the PR-VEP latencies, our DRCD-VEP data show that the visual cortex is remarkably ready to accept environmental stimulation right after birth. This early plasticity makes full use of the available extra stimulation time in preterm human infants and results in an early onset of cortical binocularity. According to our data, the developmental processes preceding the onset of binocular function are not preprogrammed, and the mechanisms turning on stereopsis are extremely experience-dependent in humans.

Contrast independence of dynamic random dot correlogram evoked VEP amplitude.

Dynamic random dot correlograms (DRDCs) are binocular stimuli that evoke a percept and a visual evoked potential (VEP) only in case of a mature and functional binocular system. DRDC-VEP is a method extensively used to study cortical binocularity in human infants and nonverbal children. Although the DRDC-VEP was invented 3 decades ago, neither the fundamental parameters, including contrast, of the stimulation nor the cerebral processing mechanisms have been clarified. The objective of the present study was to investigate the variability and detectability of adults' VEPs to DRDC under different stimulus contrast conditions. DRDCs were presented on the red and green channels of a computer monitor and were viewed with red-green goggles. The steady state DRDC-VEPs were recorded in healthy adult volunteers, and response reliability was assessed by the T(circ)(2) statistic. DRDC-VEP amplitude was independent of contrast, while VEP phases showed a weak correlation with contrast. Contrast invariance of DRDC-VEP amplitude suggests a very high contrast gain and dominant magnocellular input to the binocular correlation processing system.

Functional architecture of retinotopy in visual association cortex of behaving monkey.

While the receptive field properties of single neurons in the inferior parietal cortex have been quantitatively described from numerous electrical measurements, the visual topography of area 7a and the adjacent dorsal prelunate area (DP) remains unknown. This lacuna may be a technical byproduct of the difficulty of reconstructing tens to hundreds of penetrations, or may be the result of varying functional retinotopic architectures. Intrinsic optical imaging, performed in behaving monkey for extended periods of time, was used to evaluate retinotopy simultaneously at multiple positions across the cortical surface. As electrical recordings through an implanted artificial dura are difficult, the measurement and quantification of retinotopy with long-term recordings was validated by imaging early visual cortex (areas V1 and V2). Retinotopic topography was found in each of the three other areas studied within a single day's experiment. However, the ventral portion of DP (DPv) had a retinotopic topography that varied from day to day, while the more dorsal aspects (DPd) exhibited consistent retinotopy. This suggests that the dorsal prelunate gyrus may consist of more than one visual area. The retinotopy of area 7a also varied from day to day. Possible mechanisms for this variability across days are discussed as well as its impact upon our understanding of the representation of extrapersonal space in the inferior parietal cortex.

Measuring surface achromatic color: toward a common measure for increments and decrements.

Surface color is traditionally measured by matching methods. However, in some conditions, the color of certain surfaces cannot be measured: The surface simply looks brighter or darker than all the patches on a matching scale. We studied the reliability, validity, and range of application of three different types of simulated Munsell scales (white-, black-, and split-surrounded) as methods for measuring surface colors in simple disk-ring displays. All the scales were equally reliablefor matching both increments and decrements, but about 2096 of the increments were unmatchable on the white-surrounded scale, about 1396 of the decrements were unmatchable on the black-surrounded scale, and about 9% of the increments were unmatchable on the split-surrounded scale. However, matches on all the scales were linearly related. Therefore, it is possible to convert them to common units, using regression parameters. These units provide an extended metric for measuring all increments and decrements in the stimulus space, effectively removing ceiling and floor effects, and providing measures even for surfaces that were perceived as out of range on some of the scales.

Functional architecture of eye position gain fields in visual association cortex of behaving monkey.

In the behaving monkey, inferior parietal lobe cortical neurons combine visual information with eye position signals. However, an organized topographic map of these neurons' properties has never been demonstrated. Intrinsic optical imaging revealed a functional architecture for the effect of eye position on the visual response to radial optic flow. The map was distributed across two subdivisions of the inferior parietal lobule, area 7a and the dorsal prelunate area, DP. Area 7a contains a representation of the lower eye position gain fields while area DP represents the upper eye position gain fields. Horizontal eye position is represented orthogonal to the vertical eye position across the medial lateral extents of the cortices. Similar topographies were found in three hemispheres of two monkeys; the horizontal and vertical gain field representations were not isotropic with a greater modulation found with the vertical. Monte Carlo methods demonstrated the significance of the maps, and they were verified in part using multiunit recordings. The novel topographic organization of this association cortex area provides a substrate for constructing representations of surrounding space for perception and the guidance of motor behaviors.