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The mammalian brain can take into account the neural delays in visual information transmission from the retina to the cortex when accurately localizing the instantaneous position of moving objects by motion extrapolation. In this study, we wanted to investigate whether such extrapolation mechanism operates in a comparable fashion between the eyes in normally sighted and amblyopic observers.To measure interocular extrapolation, we adapted a dichoptic version of the flash-lag effect (FLE) paradigm, in which a flashed bar is perceived to lag behind a moving bar when their two positions are physically aligned. Twelve adult subjects with amblyopia and 12 healthy controls participated in the experiment. We measured the FLE magnitude of the subjects under binocular, monocular, and dichoptic conditions.In controls, the FLE magnitude of binocular condition was significantly smaller than that of monocular conditions (P ≤ 0.023), but there was no difference between monocular and dichoptic conditions. Subject with amblyopia exhibited a smaller FLE magnitude in the dichoptic condition when the moving bar was presented to the amblyopic eye and the flash to the fellow eye (DA condition) compared to the opposite way around (DF condition), consistent with a delay in the processing of the amblyopic eye (P = 0.041).Our observations confirm that trajectory extrapolation mechanisms transfer between the eyes of normal observers. However, such transfer may be impaired in amblyopia. The smaller FLE magnitude in DA compared to DF in patients with amblyopia could be due to an interocular delay in the amblyopic visual system. The observation that normal controls present a smaller FLE in binocular conditions raises the question whether a larger FLE is or is not an indicator of better motion processing and extrapolation.

Neural selectivity of orientation is a fundamental property of visual system. We aim to investigate whether and how the orientation selectivity changes in amblyopia.Seventeen patients with amblyopia (27.1 ± 7.1 years) and 18 healthy participants (25.1 ± 2.7 years) took part in this study. They were asked to continuously detect vertical gratings embedded in a stream of randomly oriented gratings. Using a technique of subspace reverse correlation, the orientation-time perceptive field (PF) for the atypical grating detection task was derived for each participant. Detailed comparisons were made between the PFs measured with the amblyopic and healthy eyes.The PF of the amblyopic eyes showed significant differences in orientation and time domain compared with that of the normal eyes (cluster-based permutation test, ps0.05), with broader bandwidth of orientation tuning (31.41 ± 10.59 degrees [mean ± SD] vs. 24.76 ± 6.85 degrees, P = 0.039) and delayed temporal dynamics (483 ± 68 ms vs. 425 ± 58 ms, P = 0.015). None of the altered PF properties correlated with the contrast sensitivity at 1 cycle per degree (c/deg) in amblyopia. No difference in PFs between the dominant and non-dominant eyes in the healthy group was found.The altered orientation-time PF to the low spatial frequency and high contrast stimuli suggests amblyopes had coarser orientation selectivity and prolonged reaction time. The broader orientation tuning probably reflects the abnormal lateral interaction in the primary visual cortex, whereas the temporal delay might indicate a high level deficit.

Amblyopia is a major health problem with an estimated 2% to 4% of the population affected. Screening combined with corrective measures, such as correction of refractive error and occlusion of the dominant eye, could reduce this prevalence. A new pediatric vision scanner, the blinq (Rebion, Boston, MA), studies the foveolar quality of fixation of each eye during binocular viewing. Based on the initial premise that poor quality foveolar or non-foveolar fixation is indicative of strabismus and, potentially of amblyopia, this study evaluates the effectiveness of the blinq screening device in detecting these two conditions compared to a standard ophthalmic examination (Gold Standard) based on the recommendations of the American Association for Pediatric Ophthalmology and Strabismus.A prospective study was performed on a total of 101 children between 2 and 8 years of age. These children were offered a test by the blinq screening device before a standard ophthalmological examination in the ophthalmology department of the Erasmus Hospital in Brussels, Belgium. The two tests were then compared.In a pediatric population heightened with amblyopia and strabismus (prevalence of 33.4%) and based on the Gold Standard Examination, the blinq device showed a specificity of 73.1% (95% confidence interval [CI] = 60.9%-83.2%) with a sensitivity of 91.2% (95% CI = 76.3%-98.1) to detect these conditions. The positive and negative predictive values were 63.3% (95% CI = 53.4%-72.2%) and 94.2% (95% CI = 84.6%-98%) respectively. The positive likelihood ratio (LR+) was 3.39 (95% CI = 2.26-5.11) for a negative likelihood ratio of 0.12 (95% CI = 0.04-0.36).The blinq device has good sensitivity, but insufficient specificity to be used alone in the first line of screening. Whereas other devices on the market detect risk factors that may lead to amblyopia, the blinq pediatric vision scanner detects poor foveolar fixation and strabismus, giving it a potential advantage in sensitivity to directly detect strabismus, including microstrabismus. The blinq does not detect refractive abnormalities, however, and will therefore need to be improved in the future to be used alone in pediatric vision screening.The blinq device detects visual axis alignment abnormalities with potential impact in the early detection of strabismus and subsequent associated amblyopia.

To determine if visual acuity (VA) outcomes are comparable using the amblyopia treatment study HOTV protocol (ATS-HOTV) and electronic Early Treatment of Diabetic Retinopathy Study (E-ETDRS) protocol in children with optic pathway gliomas (OPGs).Children enrolled in a prospective study of OPGs were eligible if they completed both the ATS-HOTV and E-ETDRS during the same visit. The contribution of age, testing order, having neurofibromatosis type 1, visual field loss, and circumpapillary retinal nerve fiber layer thickness to VA difference were assessed using generalized estimating equations to account for the intereye correlation.Forty-eight children (median age, 10.3 years; range, 5.2-17.1 years; 49% female) met inclusion criteria and contributed 93 study eyes at their initial visit. Eleven patients (22 eyes) had more than one study visit, permitting longitudinal evaluation. ATS-HOTV measures of VA were higher than E-ETDRS at the initial (0.13 ± 0.36 vs. 0.23 ± 0.39 logarithm of the minimum angle of resolution [logMAR], P0.001) and all visits (0.13 ± 0.34 vs. 0.21 ± 0.36 logMAR, P0.001). VA remained significantly higher with ATS-HOTV regardless of test order, but the mean difference between tests was most profound when tested with ATS-HOTV first compared to E-ETDRS first (P0.001).VA results differ significantly between the ATS-HOTV and E-ETDRS testing methods in children with OPGs. Given the wide range of ages and testing ability of children, one VA testing method should be used throughout longitudinal OPG clinical trials.It is imperative that age-appropriate VA testing methods are standardized across all pediatric OPG clinical trials.

Patients with amblyopia are known to have fixation instability, which arises from alteration of physiologic fixation eye movements (FEMs) and nystagmus. We assessed the effects of monocular, binocular, and dichoptic viewing on FEMs and eye alignment in patients with and without fusion maldevelopment nystagmus (FMN).Thirty-four patients with amblyopia and seven healthy controls were recruited for this study. Eye movements were recorded using infrared video-oculography during (1) fellow eye viewing (FEV), (2) amblyopic eye viewing (AEV), (3) both eye viewing (BEV), and (4) dichoptic viewing (DcV) at varying fellow eye (FE) contrasts. The patients were classified per the clinical type of amblyopia and FEM waveforms into those without nystagmus, those with nystagmus with and without FMN. Fixational saccades and intersaccadic drifts, quick and slow phases of nystagmus, and bivariate contour ellipse area were analyzed in the FE and amblyopic eye (AE).We found that FEMs are differentially affected with increased amplitude of quick phases of FMN observed during AEV than BEV and during DcV at lower FE contrasts. Increased fixation instability was seen in anisometropic patients at lower FE contrasts. Incomitance of eye misalignment was seen with the greatest increase during FEV. Strabismic/mixed amblyopia patients without FMN were more likely to demonstrate a fixation switch where the AE attends to the target during DcV than patients with FMN.Our findings suggest that FEM abnormalities modulate with different viewing conditions as used in various amblyopia therapies. Increased FEM abnormalities could affect the visual function deficits and may have treatment implications.

Purpose To assess whether monocular contrast sensitivity and stereoacuity impairments remain when visual acuity is fully recovered in children with refractive amblyopia. Methods A retrospective review of 487 patients diagnosed with refractive amblyopia whose visual acuity improved to 0.08 logMAR or better in both eyes following optical treatment was conducted. Measurements of monocular contrast sensitivity and stereoacuity had been made when visual acuity normalized. All patients had been treated with refractive correction for approximately 2 years following diagnosis. No other treatments were provided. Monocular contrast sensitivity was measured using the CSV-1000E chart for children 6 years of age or younger and a psychophysical technique called the quick contrast sensitivity function in older children. Stereoacuity was measured using the Random Dot Test that includes monocular cues and the Randot Stereoacuity Test that does not have monocular cues. Results Statistically significant interocular differences in contrast sensitivity were observed. These differences tended to occur at higher spatial frequencies (12 and 18 cycles per degree). Stereoacuity within the age-specific normal range was achieved by 47.4% of patients for the Random Dot Test and only 23.1% of patients for the Randot Stereoacuity Test. Conclusions Full recovery of visual acuity following treatment for refractive amblyopia does not equalize interocular contrast sensitivity or restore normal stereopsis. Alternative therapeutic approaches that target contrast sensitivity and/or binocular vision are required.

Idiopathic infantile nystagmus syndrome is a disorder characterised by involuntary eye movements, which leads to decreased acuity and visual function. One such function is visual crowding - a process whereby objects that are easily recognised in isolation become impaired by nearby flankers. Crowding typically occurs in the peripheral visual field, although elevations in foveal vision have been reported in congenital nystagmus, similar to those found with amblyopia. Here, we examine whether elevated foveal crowding with nystagmus is driven by similar mechanisms to those of amblyopia - long-term neural changes associated with a sensory deficit - or by the momentary displacement of the stimulus through nystagmus eye movements. A Landolt-C orientation identification task was used to measure threshold gap sizes with and without either horizontally or vertically placed Landolt-C flankers. We assume that a sensory deficit should give equivalent crowding in these two dimensions, whereas an origin in eye movements should give stronger crowding with horizontal flankers given the predominantly horizontal eye movements of nystagmus. We observe elevations in nystagmic crowding that are above crowding in typical vision but below that of amblyopia. Consistent with an origin in eye movements, elevations were stronger with horizontal than vertical flankers in nystagmus, but not in typical or amblyopic vision. We further demonstrate the same horizontal elongation in typical vision with stimulus movement that simulates nystagmus. Consequently, we propose that the origin of nystagmic crowding lies in the eye movements, either through image smear of the target and flanker elements or through relocation of the stimulus into the peripheral retina.

Purpose This study aimed to custom design, build, and test a removable device that accurately and objectively monitors adherence to spectacle wear in preschool children participating in clinical trials. This work will provide researchers with the tools to investigate the effect of adherence to optical treatment in conditions relating to refractive error, such as anisometropia, amblyopia, myopia, and accommodative esotropia, where spectacle wearing behaviors are of interest. Methods Several sensors were considered in the design of the SpecsOn monitor. The final version included two temperature sensors, one that measures skin temperature through an infrared sensor directed at the wearer's temple on the spectacle arm and the other measuring device temperature. The difference between the two temperature readings is used to determine if the spectacles were worn. The SpecsOn monitor was tested in two phases in adult participants (laboratory n = 10 and real world n = 5). Results Results from both phases showed good agreement between the objective measurement of wear based on skin and device temperature differences and participants’ manually logged wear times. The custom built SpecsOn monitor was 99% successful in accurately detecting spectacle wear in our adult cohort. Conclusions The SpecsOn monitor offers a convenient, accurate, and reliable system to monitor spectacle adherence. The devices were comfortable, secure, and unobtrusive to wear, and fitted easily to a variety of frame styles. Translational Relevance Easy access to spectacle compliance information from the SpecsOn monitor during the optical treatment phase will optimize visual outcomes and provide detailed clinical data to support decision making on the need and timing of additional therapies, improving treatment efficiency.

Purpose Synaptosomal actin dynamics are essential for synaptic structural stability. Whether actin dynamics are involved in structural and functional synaptic plasticity within the primary visual cortex (V1) or behavioral visual acuity in rats has still not been thoroughly investigated. Methods Synaptosome preparation and western blot analysis were used to analyze synaptosomal actin dynamics. Transmission electron microscopy was used to detect synaptic density and mitochondrial area alterations. A visual water maze task was applied to assess behavioral visual acuity. Microinjection of the actin polymerization inhibitor or stabilizer detected the effect of actin dynamics on visual function. Results Actin dynamics, the mitochondrial area, and synaptic density within the area of V1 are increased during the critical period for the development of binocularity. Microinjection of the actin polymerization inhibitor cytochalasin D into the V1 decreased the mitochondrial area, synaptic density, and behavioral visual acuity. Long-term monocular deprivation reduced actin dynamics, the mitochondrial area, and synaptic density within the V1 contralateral to the deprived eye compared with those ipsilateral to the deprived eye and impaired visual acuity in the amblyopic eye. In addition, the mitochondrial area, synaptic density, and behavioral visual acuity were improved by stabilization of actin polymerization by jasplakinolide microinjection. Conclusions During the critical period of visual development of binocularity, synaptosomal actin dynamics regulate synaptic structure and function and play roles in behavioral visual acuity in rats.

Purpose Dichoptic training is becoming a popular tool in amblyopia treatment. Here we investigated the effects of dichoptic demasking training in children with amblyopia who never received patching treatment (NPT group) or were no longer responsive to patching (PT group). Methods Fourteen NPT and thirteen PT amblyopes (6–16.5 years; 24 anisometropic, two strabismus, and one mixed) received dichoptic demasking training for 17 to 22 sessions. They used the amblyopic eye (AE) to practice contrast discrimination between a pair of Gabors that were dichoptically masked by a band-filtered noise pattern simultaneously presented in the fellow eye (FE). Dichoptic learning was quantified by the increase of maximal tolerable noise contrast (TNC) for AE contrast discrimination. Computerized visual acuities and contrast sensitivity functions for both eyes and the Randot stereoacuity were measured before and after training. Results Training improved maximal TNC by six to eight times in both groups, along with a boost of AE acuities by 0.15 logMAR (P < 0.001) in the NPT group and 0.06 logMAR (P < 0.001) in the PT group. This visual acuity improvement was significantly dependent on the pretraining acuity. Stereoacuity was significantly improved by 41.6% (P = 0.002) in the NPT group and 64.2% (P < 0.001) in the PT group. The stereoacuity gain was correlated to the pretraining interocular acuity difference (r = −0.49, P = 0.010), but not to the interocular acuity difference change (r = −0.28, P = 0.15). Training improved AE contrast sensitivity in the NPT group (P = 0.009) but not the PT group (P = 0.76). Moreover, the learning effects in 12 retested observers were retained for 10 to 24 months. Conclusions Dichoptic training can improve, and sometimes even restore, the stereoacuity of amblyopic children, especially those with mild amblyopia (amblyopic VA ≦0.28 logMAR). The dissociation of stereoacuity gain and the interocular acuity difference change suggests that the stereoacuity gain may not result from a reduced interocular suppression in most amblyopes. Rather, the amblyopes may have learned to attend to, or readout, the stimulus information to improve stereopsis.

Purpose Eccentric fixation in amblyopia is often estimated grossly without precision. Although the usefulness of optical coherence tomography (OCT) fixation shift in the quantification of eccentric fixation in a small cohort of amblyopic children was recently reported, there is a lack of understanding of characteristics of OCT fixation shift. In a retrospective cohort study, we evaluated eccentric fixation with OCT in a large cohort of children with residual amblyopia. Methods Children, age 4 to 17 years, with residual amblyopia (amblyopic, n = 56) and without amblyopia (control, n = 75) were enrolled. Amblyopia was associated with anisometropia alone (anisometropia subtype, n = 28) and strabismus without or with anisometropia (strabismic subtype, n = 28). Spectral domain OCT was used to estimate fixation. The OCT fixation shift, defined as the distance between the fovea and the fixation point, was measured and adjusted with calculated axial length and converted into visual degrees. Fixation shift in amblyopic eyes, fellow nonamblyopic eyes, and right eyes of the control group were compared. Fixation shift between the anisometropic and strabismic amblyopia subtypes was also compared. Its correlation with visual acuity was estimated. Results The mean fixation shift was significantly different: 0.17° ± 0.29° for control right eyes, 0.94° ± 1.24° for amblyopic eyes, and 0.34° ± 0.57° for fellow eyes (χ2 = 23.3; P < 0.001). There was no significant difference between fellow eyes and control eyes (P = 0.11). Fixation shift in amblyopic eyes was significantly correlated with visual acuity (R = 0.44; P < 0.001), and it was significantly smaller in the anisometropic subtype than in the strabismic subtypes (0.34° ± 0.46° vs. 1.54° ± 1.48°, W = 338, P < 0.001). Conclusions OCT fixation shift can be used both in detection and quantification of eccentric fixation in children with residual amblyopia, especially in those with strabismus. Translational Relevance OCT fixation shift offers a convenient clinical approach in quantitative evaluation of eccentric fixation in children with strabismic amblyopia.

Purpose To study binocular balance by comparing dichoptic and standard monocular contrast sensitivity function (CSF) in stereonormal and stereoanomalous/stereoblind amblyopic subjects. Methods Sixteen amblyopes and 17 controls participated. Using the capability of the passive three-dimensional display, we measured their CSF both monocularly and dichoptically at spatial frequencies 0.5, 1, 2, 4, and 8 cpds using achromatic Gabor patches on a luminance noise background. During monocular stimulation, the untested eye was covered, while for the dichoptic stimulation the untested eye viewed background noise. Dichoptic CSF of both eyes was acquired within one block. Results In patients with central fixation, dichoptic viewing had a large negative impact on the CSF of the amblyopic eye, although it hardly affected that of the dominant eye. In contrast, dichoptic viewing had a small but significant effect on both eyes for controls. In addition, all participants lay along a continuum in terms of how much their two eyes were affected by dichoptic stimulation: by using two predefined contrast sensitivity ratios, namely, amblyopic sensitivity decrement and dichoptic sensitivity decrement, not only did we find a significant correlation between these variables among all participants, but also the two groups were identified with minimum error using a cluster analysis. Conclusions Dichoptic CSF may be considered to measure visual performance in patients with altered binocular vision, because it better reflects the visual capacity of the amblyopic eye than the standard monocular examinations. It may also be a more reliable parameter to assess the efficacy of modern approaches to treat amblyopia.

Purpose During binocular viewing, many strabismic subjects choose the eye of fixation depending on the retinotopic location of a visual target. Here, we compare eye choice behavior when orienting to visual and non-visual (auditory) targets. Methods Eye movements were measured in two head-fixed exotropic strabismic monkeys in a saccadic task involving either a visual or an auditory stimulus (no visual target information or feedback) during monocular or binocular viewing. The stimulus was one of 21 visual or auditory targets arranged 10° apart in a 7 × 3 array at a distance of 57 cm in an otherwise dark room. Fixation preference was calculated by recording the incidence of using a specific eye to acquire the target at any location. Results Spatial patterns of fixation preference were observed in both monkeys for both visual and auditory stimuli; targets to the far right were acquired by the right eye, and targets to the far left were acquired by the left eye. For visual targets, the border for a change in fixation preference occurred in between the visual axes of the fixating and deviated eyes (variable in the two animals). In contrast, the border for fixation change remained near the cranio-center during the auditory task. During monocular viewing, fixation switching was observed only at the extremities during visual tasks; during the auditory task, fixation preference was similar to that observed during binocular viewing. Conclusions Fixation preference persists for invisible auditory targets. Our data suggest that visual suppression could modify underlying eye choice behavior that functions independently from vision.

Purpose To investigate the influence of interocular suppression and visual acuity loss on stereoacuity in observers with and without abnormal vision development from strabismus or amblyopia. To determine whether stereoacuity improves in amblyopic observers when suppression is neutralized. Methods Experiment 1: Visual acuity (VA), depth of suppression (contrast ratio [CR]), and stereoacuity (digital random-dot) were tested in adult amblyopic observers (n = 21; age 27 ± 11 years). Experiment 2: VA, stereoacuity, and CR were measured at baseline and through a series of monocular contrast attenuation and Bangerter filter conditions that degrade visual input in participants with normal binocular vision (n = 19; age 31 ± 13 years). Multiple regression models were used to determine relative contribution of VA and CR to stereoacuity in both groups. Experiment 3: stereoacuity was retested in a subsample of amblyopic observers (n = 7) after contrast reduction of the stimulus presented to dominant eye to neutralize suppression. Results In amblyopic observers, stereoacuity significantly correlated with CR (P < 0.001), but not with interocular VA difference (P = 0.863). In participants with normal vision development, stereoacuity, VA, and CR declined with introduction of monocular Bangerter filter (P < 0.001), and stereoacuity reduced with monocular attenuation of stimulus contrast (P < 0.001). Reduction in stereoacuity correlated with both VA decrement and degraded CR. Stereoacuity significantly improved in amblyopic observers when the contrast to the dominant eye was adjusted based on the contrast ratio. Conclusions Suppression rather than visual acuity loss limits stereoacuity in observers with abnormal vision development. Stereopsis can be improved when interocular sensory dominance is neutralized.

Purpose Global motion and global form perception have been found to be abnormal in the presence of amblyopia. How such deficits manifest in visual function reliant on the interactions between these two visual processing mechanisms has not been adequately explored. In the current study, we use dynamic Glass patterns (dGlass) to measure implied motion thresholds in variable external noise to investigate the local and global limitations of processing. Methods A total of 13 amblyopes (eight strabismic and five anisometropic, mean interocular visual acuity difference 0.30 ± 0.12 logMAR) and six visually normal controls discriminated the overall implied motion of dGlass generated by presenting nine independent sets of static Glass patterns over 0.5 seconds. The orientation of dipole elements was derived from the Gaussian distribution with prescribed mean and standard deviation that served as external noise. Thresholds at varying external noise were fitted to a set of linear amplifier models that were statistically compared to investigate the contribution of local and global processing parameters. Results The implied motion thresholds were higher for strabismic (4.33° ± 1.34°) compared to anisometropic (2.32° ± 0.76°) amblyopia and controls (2.28° ± 0.50°) in the no-noise condition. The multivariate ANOVA analysis showed no difference between amblyopic and control observers at the no-noise and high-noise levels (P > 0.1). The statistical comparison of nested models showed normal internal noise and sampling efficiency parameters for both strabismic and anisometropic amblyopia (PS >0.50). Conclusions The normal thresholds for implied motion in this study would suggest that motion aids the perception of global form cues present in dynamic Glass patterns. Our results challenge the proposed dorsal stream vulnerability in developmental disorders such as amblyopia.

Purpose While using their amblyopic eye, individuals with strabismic amblyopia count inaccurately and underestimate the number of features. These deficits are attributed to limitations in high-level cortical functions and attention. In the current study, we examined whether feature counting is affected in strabismic and anisometropic amblyopia during dichoptic viewing, a setup that can better capture binocular function disruptions. Methods Through a mirror stereoscope, Gabor patches were presented for 200 msec (Experiment 1) or 350 msec (Experiment 2) in both the left eye and the right eye of observers, who were required to combine the percepts and report the total number of patches. Counting performance and errors were compared across amblyopic groups and normal-sighted observers. The contribution and relation of each eye to performance was also evaluated. Results Anisometropic and strabismic amblyopia groups counted inaccurately and underestimated the number of features compared to the normal-sighted group. In both amblyopic groups, the amblyopic eye contributed less in comparison to the fellow eye. The strabismic group exhibited worse performance, and a more pronounced difference in eye contribution, in comparison to the anisometropic group. Conclusions Overall, our results support the view of higher-level cortical and binocular function deficits in amblyopia. Translational relevance The current study bridges the gap between research on high-cortical function deficits and clinical binocular function disruptions in amblyopia, which can help us better understand the neural mechanism of amblyopia and inform clinical therapeutic tasks and strategies.

Purpose: We investigated and characterized the patterns of meridional anisotropies in newly diagnosed refractive amblyopes using pattern onset–offset visual evoked potentials (POVEPs) and psychophysical grating acuity (GA).\ud \ud Methods: Twenty-five refractive amblyopes were recruited and compared with non-amblyopic controls from our previous study. Monocular POVEPs were recorded in response to sinewave 4 cycles per degree (cpd) grating stimuli oriented along each individual participants' principal astigmatic meridians, which were approximately horizontal (meridian 1) and vertical (meridian 2). Binocular POVEPs in response to the same stimuli, but oriented at 45°, 90°, 135°, and 180°, were recorded. Psychophysical GAs were assessed along the same meridians using a two-alternative non-forced-choice technique. The C3 amplitudes and peak latencies of the POVEPs and GAs were compared across meridians for both groups (refractive amblyopes and controls) using linear mixed models (monocular) and ANOVA (binocular), and post hoc analysis was conducted to determine if meridional anisotropies in this cohort of amblyopes were related to low (≤1.50 diopters [D]), moderate (1.75–2.75 D) and high (≥3.00 D) astigmatism.\ud \ud Results: In the newly diagnosed refractive amblyopes, there were no significant meridional anisotropies across all outcome measures, but the post hoc analysis demonstrated that C3 amplitude was significantly higher in those with low (P = 0.02) and moderate (P = 0.004) astigmatism compared to those with high astigmatism. Refractive amblyopes had poorer GA and C3 amplitudes compared to controls by approximately two lines on the logMAR chart (monocular: P = 0.013; binocular: P = 0.014) and approximately 6 µV (monocular: P = 0.009; binocular: P = 0.027), respectively.\ud \ud Conclusions: Deleterious effects of high astigmatism was evident in newly diagnosed refractive amblyopes, but the neural deficits do not seem to be orientation-specific for the stimulus parameters investigated.

Amblyopia is a cortical visual disorder caused by unequal visual input to the brain from the two eyes during development. Amblyopes show reduced visual acuity and contrast sensitivity and abnormal binocularity, as well as more "global" perceptual losses, such as figure-ground segregation and global form integration. Currently, there is no consensus on the neural basis for these higher-order perceptual losses. One contributing factor could be that amblyopes have deficiencies in attention, such that the attentional processes that control the selection of information favor the better eye. Previous studies in amblyopic adults are conflicting as to whether attentional deficits exist. However, studies where intact attentional ability has been shown to exist were conducted in adults; it is possible that it was acquired through experience. To test this hypothesis, we studied attentional processing in amblyopic children. We examined covert endogenous attention using a classical spatial cueing paradigm in amblyopic and visually typical 5- to 10-year old children. We found that all children, like adults, independently of visual condition, benefited from attentional cueing: They performed significantly better on trials with an informative (valid) cue than with the uninformative (neutral) cue. Response latencies were also significantly shorter for the valid cue condition. No statistically significant difference was found between the performance of the amblyopic and the visually typical children or between dominant and nondominant eyes of all children. The results showed that covert spatial attention is intact in amblyopic and visually typical children and is therefore not likely to account for higher-order perceptual losses in amblyopic children.

Purpose To assess interocular delays in amblyopes with stereopsis and to evaluate the relationship between interocular delays and the clinical characteristics. Methods Twenty amblyopes with stereopsis (median, 400 arcseconds) and 20 controls with normal or corrected to normal visual acuity (≤0 logMAR) and normal stereopsis (≤60 arcseconds) participated. Using a rotating cylinder defined by horizontally moving Gabor patches, we produced a spontaneous Pulfrich phenomenon in order to determine the interocular delays, that is, the interocular phase difference at which ambiguous motion in plane was perceived. Two spatial frequencies—a low (0.95 cycles/degree [c/d]) and a medium (2.85 c/d) spatial frequency—were tested. Results The absolute interocular delays of the amblyopic group was significantly longer than that of the controls at both low or medium spatial frequencies (P < 0.01). However, the interocular delays was not always in favor of the fellow eye: 35% of the amblyopes (7/20) showed a faster processing of the amblyopic eye than that of the fellow eye at 0.95 c/d and 29.5% (5/17) at 2.85 c/d. No significant correlation was found between interocular delays and the clinical characteristics (e.g., age, treatment history, stereoacuity, and magnitude of anisometropia) in this amblyopic cohort. Conclusions The interocular delays in amblyopes with stereopsis might result from either a faster or slower processing of the amblyopic eye relative to the fellow eye. This work provides important additional information for binocular processing of dynamic visual stimuli in amblyopia. However, the special role between this form of interocular delays and patients’ clinical characteristics remains unknown.

Purpose Optical treatment can improve visual function in anisometropic amblyopia, but there is no electrophysiological evidence, and the underlying change in visual pathway remains unknown. Our aims were to characterize the functional loss in magnocellular and parvocellular visual pathways in anisometropic amblyopia at baseline and to investigate the effect of optical treatment on the 2 visual pathways. Methods Using isolated-check visual-evoked potential, we measured the magnocellular- and parvocellular-biased contrast response functions in 15 normal controls (20.13 ± 3.93 years; mean ± standard deviation), 16 patients with anisometropic amblyopia (18.00 ± 6.04 years) who were fully refractive corrected before and 29 (19.41 ± 7.41 years) who had never been corrected. Twelve previously uncorrected amblyopes received optical treatment for more than 2 months and finished the follow-up measurement. Results Both the magnocellular- and parvocellular-biased contrast response functions in the amblyopic eye exhibited significantly reduced response and weaker contrast gains. We also found that the uncorrected amblyopes showed a more severe response reduction in magnocellular-biased, but not parvocellular-biased condition when compared with those corrected, with a weaker initial contrast gain and lower maximal response. After optical treatment, 12 uncorrected amblyopes demonstrated improved visual acuity of the amblyopic eye and a significant response gain to magnocellular-biased but not parvocellular-biased stimuli. Conclusions We demonstrated deficits to both magnocellular- and parvocellular-biased stimuli in subjects with anisometropic amblyopia. Optical treatment could produce neurophysiological changes in visual pathways even in older children and adults, which may be mediated through the magnocellular pathway.

Purpose To demonstrate an aniseikonia test for anisometropic amblyopia (ATAA) that uses variable viewing luminance at different interocular contrast levels. Methods The test consists of a direct size comparison task based on a computer. The subject is asked to adjust the size of a dichoptically dissociated paired square target. One square was always presented at 100% contrast to the amblyopic eye/nondominant eye, whereas its counterpart was presented to the fellow eye at six contrast levels. Measurements were performed at two luminance backgrounds: (1) a white square on a black background (WoB) and (2) a black square on a white background (BoW). To test the feasibility of this approach, 16 patients with anisometropic amblyopia and 23 normal controls were recruited. Results The Aniseikonia Index (AI) calculated from the ATAA increased when the difference in the interocular contrast increased in both the patients with anisometropic amblyopia and controls under BoW and WoB conditions. The mean AI differed dramatically between the BoW and WoB conditions in patients with amblyopia but not in normal subjects. Conclusions Our model predicted interocular differences in contrast to the measurement of aniseikonia. Execution of the AI in individuals with amblyopia should consider that their responses to different luminance viewing conditions could be asymmetric. Translational relevance The ATAA has the potential to optimize optical correction for the management of aniseikonia in individuals with anisometropic amblyopia.

The purpose of this study was to compare the accommodative performance of the amblyopic eye of children with unilateral amblyopia to that of their nonamblyopic eye, and also to that of children without amblyopia, during both monocular and binocular viewing.Modified Nott retinoscopy was used to measure accommodative performance of 38 subjects with unilateral amblyopia and 25 subjects with typical vision from 3 to 13 years of age during monocular and binocular viewing at target distances of 50, 33, and 25 cm. The relationship between accommodative demand and interocular difference (IOD) in accommodative error was assessed in each group.The mean IOD in monocular accommodative error for amblyopic subjects across all three viewing distances was 0.49 diopters (D) (95% confidence interval [CI], ±1.12 D) in the 180° meridian and 0.54 D (95% CI, ±1.27 D) in the 90° meridian, with the amblyopic eye exhibiting greater accommodative errors on average. Interocular difference in monocular accommodative error increased significantly with increasing accommodative demand; 5%, 47%, and 58% of amblyopic subjects had monocular errors in the amblyopic eye that fell outside the upper 95% confidence limit for the better eye of control subjects at viewing distances of 50, 33, and 25 cm, respectively.When viewing monocularly, children with unilateral amblyopia had greater mean accommodative errors in their amblyopic eyes than in their nonamblyopic eyes, and when compared with control subjects. This could lead to unintended retinal image defocus during patching therapy for amblyopia.

PURPOSE: Saccadic adaptation is affected by the spatial variability of the adapting error signal. Recently, we have shown that saccadic adaptation is reduced in anisometropic amblyopia, possibly impacted by spatially imprecise saccades. Here, we tested this idea by quantifying the saccadic endpoint variability difference between people with anisometropic amblyopia and visually normal individuals. We then applied this difference to the second target step distribution during saccadic adaptation in visually normal people to test whether their performance diminished to a similar extent as participants with amblyopia. METHODS: Ten visually normal adults performed a double-step adaptation task (±19°, followed by 4° back-steps) with the nondominant eye under two conditions: "consistent error," using a constant back-step; and "variable error," using a variable (σdiff) back-step determined by subtracting the saccadic endpoint variability in controls from that in anisometropic amblyopia during amblyopic/nondominant eye viewing. Percentage change in saccadic gains, percentage retention, and adaptation time constants were analyzed. RESULTS: Percentage change in saccadic gains decreased significantly during the variable error condition (50% ± 10%) compared to the consistent error condition (69% ± 9%; P = 0.0008). Percentage retention and time constants did not differ between conditions. The adaptation magnitude during the variable error condition was comparable to the previous percentage adaptation in people with anisometropic amblyopia during the consistent error condition with amblyopic eye viewing. CONCLUSIONS: Our findings indicate that adding exogenous spatial noise to the adapting step consistent with the saccadic endpoint variability difference between amblyopic and visually normal groups is sufficient to reduce saccadic adaptation in healthy individuals.

PURPOSE To examine the effects of strabismic amblyopia and strabismus only, without amblyopia, on the temporal patterns of eye-hand coordination during both the planning and execution stages of visually-guided reaching. METHODS Forty-six adults (16 with strabismic amblyopia, 14 with strabismus only, and 16 visually normal) executed reach-to-touch movements toward targets presented randomly 5° or 10° to the left or right of central fixation. Viewing conditions were binocular, monocular viewing with the amblyopic eye, and monocular viewing with the fellow eye (dominant and nondominant viewing for participants without amblyopia). Temporal coordination between eye and hand movements was examined during reach planning (interval between the initiation of saccade and reaching, i.e., saccade-to-reach planning interval) and reach execution (interval between the initiation of saccade and reach peak velocity [PV], i.e., saccade-to-reach PV interval). The frequency and dynamics of secondary reach-related saccades were also examined. RESULTS The temporal patterns of eye-hand coordination prior to reach initiation were comparable among participants with strabismic amblyopia, strabismus only, and visually normal adults. However, the reach acceleration phase of participants with strabismic amblyopia and those with strabismus only were longer following target fixation (saccade-to-reach PV interval) than that of visually normal participants (P < 0.05). This effect was evident under all viewing conditions. The saccade-to-reach planning interval and the saccade-to-reach PV interval were not significantly different among participants with amblyopia with different levels of acuity and stereo acuity loss. Participants with strabismic amblyopia and strabismus only initiated secondary reach-related saccades significantly more frequently than visually normal participants. The amplitude and peak velocity of these saccades were significantly greater during amblyopic eye viewing in participants with amblyopia who also had negative stereopsis. CONCLUSIONS Adults with strabismic amblyopia and strabismus only showed an altered pattern of temporal eye-hand coordination during the reach acceleration phase, which might affect their ability to modify reach trajectory using early online control. Secondary reach-related saccades may provide a compensatory mechanism with which to facilitate the late online control process in order to ensure relatively good reaching performance during binocular and fellow eye viewing.

Purpose We assessed whether partial occlusion of the nonamblyopic eye with Bangerter filters can immediately reduce suppression and promote binocular summation of contrast in observers with amblyopia. Methods In Experiment 1, suppression was measured for 22 observers (mean age, 20 years; range, 14-32 years; 10 females) with strabismic or anisometropic amblyopia and 10 controls using our previously established "balance point" protocol. Measurements were made at baseline and with 0.6-, 0.4-, and 0.2-strength Bangerter filters placed over the nonamblyopic/dominant eye. In Experiment 2, psychophysical measurements of contrast sensitivity were made under binocular and monocular viewing conditions for 25 observers with anisometropic amblyopia (mean age, 17 years; range, 11-28 years; 14 females) and 22 controls (mean age, 24 years; range, 22-27; 12 female). Measurements were made at baseline, and with 0.4- and 0.2-strength Bangerter filters placed over the nonamblyopic/dominant eye. Binocular summation ratios (BSRs) were calculated at baseline and with Bangerter filters in place. Results Experiment 1: Bangerter filters reduced suppression in observers with amblyopia and induced suppression in controls (P = 0.025). The 0.2-strength filter eliminated suppression in observers with amblyopia and this was not a visual acuity effect. Experiment 2: Bangerter filters were able to induce normal levels of binocular contrast summation in the group of observers with anisometropic amblyopia for a stimulus with a spatial frequency of 3 cycles per degree (cpd, P = 0.006). The filters reduced binocular summation in controls. Conclusions Bangerter filters can immediately reduce suppression and promote binocular summation for mid/low spatial frequencies in observers with amblyopia.

Purpose We measure neural responses associated with form and motion processing in children with anisometropia before and after treatment with spectacles and occlusion. Methods In this prospective, case-control treatment study, 10 children with anisometropia and amblyopia and 16 age-matched visually normal children participated. Steady-state visual evoked potentials (VEP) were recorded from electrodes over the occipital cortex. The visual stimulus comprised a horizontal bar grating into which Vernier offsets were introduced and withdrawn periodically at 3.75 Hz. The VEP amplitude at 3.75 Hz (first harmonic [1F]) and 7.5 Hz (second harmonic [2F]) were recorded to index the sensitivity of form/position-sensitive versus motion/transient-sensitive neural populations, respectively. Response amplitude at 1F and 2F were recorded over a series of 10 logarithmically spaced offset sizes before and after treatment. Main outcome measures are VEP amplitude versus displacement functions, interocular response amplitude differences. Results After relaxing into spectacles (minimally-treated state), form/position-sensitive responses in the dominant/less ametropic eye of the children with anisometropia were larger and responses in the more ametropic eye were smaller than those of controls. Motion-transient responses were equal to those of controls in the less ametropic eye, but were smaller than controls in the more ametropic eye. After treatment, responses did not differ from those of controls. Conclusions Form and motion responses are differentially susceptible to neural deprivation via optical blur. Form responses are more plastic than motion responses in minimally-treated children with anisometropic amblyopia. Most treatment effects occurred above threshold range, suggesting some treatment effects are not detected clinically.

Purpose Binocular discordance due to strabismus, anisometropia, or both may result in not only monocular visual acuity deficits, but also in motion perception deficits. We determined the prevalence of fellow-eye deficits in motion-defined form (MDF) perception, the ability to identify a two-dimensional (2D) shape defined by motion rather than luminance contrast. We also examined the following: the causative role of reduced visual acuity and binocularity, associations with clinical and sensory factors, and effectiveness of binocular amblyopia treatment in alleviating deficits. Methods Participants included 91 children with residual amblyopia (strabismic, anisometropic, or both; age, 9.0 ± 1.7 years), 79 nonamblyopic children with treated strabismus or anisometropia (age, 8.5 ± 2.1 years), and 20 controls (age, 8.6 ± 1.5 years). MDF coherence thresholds, visual acuity, stereoacuity, and interocular suppression were measured. Results MDF deficits, relative to controls, were present in the fellow eye of 23% of children with residual amblyopia and 20% of nonamblyopic children. Stereoacuity and age first patched were correlated with MDF threshold (r = 0.29, 95% CI: 0.09–0.47; r = −0.33, 95% CI: −0.13 to −0.50, respectively). MDF deficits were more common in children treated with patching alone than in those receiving contrast-rebalanced binocular treatment with games or movies (t89 = 3.46; P = 0.0008). The latter was associated with a reduction in mean fellow eye MDF threshold (t26 = 6.32, P < 0.0001). Conclusions Fellow eye MDF deficits are common and likely reflect abnormalities in binocular cortical mechanisms that result from early discordant visual experience. Binocular amblyopia treatment, which is effective in improving amblyopic eye visual acuity, appears to provide a benefit for the fellow eye.

Exposure of kittens to complete darkness for 10 days has been shown (Duffy & Mitchell, 2013) to reverse the loss of visual acuity that follows a prior period of monocular deprivation (MD). In that study, recovery of acuity in the previously deprived eye was fast despite the fact that darkness was imposed 2 months after the period of MD when kittens were 3 months old. In a later study (Holman, Duffy, & Mitchell, 2018), it was demonstrated that the same period of darkness was ineffective when it was imposed on cats about 1 year old, suggesting that dark exposure may only promote recovery when applied within an early critical period. To determine the profile of this critical period, the identical period of darkness (10 days) was imposed on kittens at various ages that had all received the same 7-day period of MD from postnatal day 30 (P30). Recovery of the acuity of the deprived eye as measured by use of a jumping stand was complete when darkness was imposed prior to P186 days, but thereafter, darkness induced progressively smaller acuity improvements and was ineffective in kittens when it began at or beyond P191 days of age. These data indicate a critical period for darkness-induced recovery with an abrupt end over a 5-day period.

Purpose Evidence from animals and blind humans suggests that early visual experience influences the developmental calibration of auditory localization. Hypothesizing that unilateral amblyopia may involve cross-modal deficits in spatial hearing, we measured the precision and accuracy of sound localization in humans with amblyopia. Methods All participants passed a standard hearing test. Experiment 1 measured sound localization precision for click stimuli in 10 adults with amblyopia and 10 controls using a minimum audible angle (MAA) task. Experiment 2 measured sound localization error (i.e., accuracy) for click train stimuli in 14 adults with amblyopia and 16 controls using an absolute sound localization task. Results In Experiment 1, the MAA (mean ± SEM) was significantly greater in the amblyopia group compared with controls (2.75 ± 0.30° vs. 1.69 ± 0.09°, P = 0.006). In Experiment 2, the overall sound localization error was significantly greater in the amblyopia group compared with controls (P = 0.047). The amblyopia group also showed significantly greater sound localization error in the auditory hemispace ipsilateral to the amblyopic eye (P = 0.036). At a location within this auditory hemispace, the magnitude of sound localization error correlated significantly with deficits in stereo acuity (P = 0.036). Conclusions The precision and accuracy of sound localization are impaired in unilateral amblyopia. The asymmetric pattern of sound localization error suggests that amblyopic vision may interfere with the development of spatial hearing via the retinocollicular pathway.

Purpose To develop a novel dichoptic optokinetic nystagmus (OKN) paradigm and investigate its effectiveness in objectively quantifying the interocular suppression in subjects with monocular amblyopia. Methods Centripetal moving gratings with different contrast ratios and constant velocity were dichoptically presented to eight monocular anisometropic amblyopes and eight normal subjects. We analyzed the OKN records with an eye tracker (EyeLink; SR-Research, Ontario, Canada) to obtain the relationship between ocular-dominance of OKN and the interocular contrast ratio by fitting power curves, and examined the correlation between the effective contrast ratio for a balanced OKN and the visual acuity of the amblyopic eye in amblyopes. Results In normal subjects, the OKN pursuit times were roughly balanced for opposite directions when stimulated with centripetal gratings of same contrast; however, in amblyopes, the OKN pursuit times of the dominant eye exceeded that of the amblyopic eye. Increasing the contrast of one eye's grating led to an increase in its OKN dominance. The OKN directional ratio (y) could be well fitted by a power function of the interocular contrast ratio (x): y = axb. Moreover, in amblyopes, the effective contrast ratio (xb) for a balanced OKN correlated significantly positively with the visual acuity of the amblyopic eye (Spearman's correlation coefficient, 0.9698). Conclusions The OKN induced by dichoptic gratings moving centripetally could be used as a reliable measure to objectively quantify the interocular suppression. This paradigm, avoiding the need for subjective report from patients, offers a promising alternative index for research on the mechanisms of amblyopia and in clinical practice.