Article

Amblyopia and the binocular approach to its Therapy

April 2015
Vision Research 114(5846)

DOI:10.1016/j.visres.2015.02.009

Authors:

University of Waterloo

There is growing evidence that abnormal binocular interactions play a key role in amblyopia. In particular, stronger suppression of the amblyopic eye has been associated with poorer amblyopic eye visual acuity and a new therapy has been described that directly targets binocular function and has been found to improve both monocular and binocular vision in adults and children with amblyopia. Furthermore, non-invasive brain stimulation techniques that alter excitation and inhibition within the visual cortex have been shown to improve vision in the amblyopic eye. The aim of this review is to summarize this previous work and interpret the therapeutic effects of binocular therapy and non-invasive brain stimulation in the context of three potential neural mechanisms; active inhibition of signals from the amblyopic eye, attenuation of information from the amblyopic eye and metaplasticity of synaptic long term potentiation and long term depression. Copyright © 2015. Published by Elsevier Ltd.

The Suppressive Basis of Ocular Dominance Changes Induced by Short-Term Monocular Deprivation in Normal and Amblyopic Adults

Article

Full-text available

Oct 2023

Purpose We aimed to study the effect of short-term monocular deprivation on the suppressive interocular interactions in normals and amblyopes by using a dichoptic masking paradigm. Methods Nine adults with anisometropic or mixed amblyopia and 10 control adults participated in our study. The contrast sensitivity in discriminating a target Gabor dichoptically masked was measured before and after 2 hours of monocular deprivation. The mask consisted of bandpass-filtered noise. Both the target and the mask were horizontally oriented at the spatial frequency of 1.31 cpd. Deprivation was achieved using an opaque patch on the amblyopic eye of amblyopes and the dominant eye of controls. Results Results were similar in both controls and amblyopes. After 2 hours of monocular deprivation, the previously patched eye showed a significant increase in contrast sensitivity under dichoptic masking, which also suggested reduced suppressive effect from the nonpatched eye. Meanwhile, the contrast sensitivity of the nonpatched eye remained almost unchanged under dichoptic masking. Conclusions We demonstrate that the ocular dominance changes induced by short-term monocular deprivation—namely, the strengthening of the deprived eye's contribution—are associated with the unilateral and asymmetric changes in suppressive interaction. The suppression from the nondeprived eye is reduced after short-term monocular deprivation. This provides a better understanding of how inverse patching (patching of the amblyopic eye) could, by reducing the suppressive drive from the normally sighted (nondeprived) eye, form the basis of a new treatment for the binocular deficit in amblyopia.

Harnessing brain plasticity to improve binocular vision in amblyopia: An evidence-based update

Article

Full-text available

Jul 2023

Amblyopia is a developmental visual disorder resulting from atypical binocular experience in early childhood that leads to abnormal visual cortex development and vision impairment. Recovery from amblyopia requires significant visual cortex neuroplasticity, i.e. the ability of the central nervous system and its synaptic connections to adapt their structure and function. There is a high level of neuroplasticity in early development and, historically, neuroplastic responses to changes in visual experience were thought to be restricted to a “critical period” in early life. However, as our review now shows, the evidence is growing that plasticity of the adult visual system can also be harnessed to improve vision in amblyopia. Amblyopia treatment involves correcting refractive error to ensure clear and equal retinal image formation in both eyes, then, if necessary, promoting the use of the amblyopic eye by hindering or reducing visual input from the better eye through patching or pharmacologic therapy. Early treatment in children can lead to visual acuity gains and the development of binocular vision in some cases; however, many children do not respond to treatment, and many adults with amblyopia have historically been untreated or undertreated. Here we review the current evidence on how dichoptic training can be used as a novel binocular therapeutic approach to facilitate visual processing of input from the amblyopic eye and can simultaneously engage both eyes in a training task that requires binocular integration. It is a novel and promising treatment for amblyopia in both children and adults.

Nonequilibrium dynamics and thermodynamics provide the underlying physical mechanism of the perceptual rivalry

Article

Full-text available

Apr 2025

Perceptual rivalry, where conflicting sensory information leads to alternating perceptions crucial for associated cognitive function, has long attracted research attention. Despite progress being made, authors of recent studies have revealed limitations and inconsistencies in our understanding across various rivalry contexts. We develop a unified physical framework, where perception undergoes a consecutive phase transition process encompassing different multistate competitions. We reveal the underlying mechanisms of perceptual rivalry by identifying dominant switching paths among perceptual states and quantifying mean perceptual durations, switching frequencies, and proportions of different perceptions. We uncover the underlying nonequilibrium dynamics and thermodynamics by analyzing average nonequilibrium flux and entropy production rate, while associated time series irreversibility reflects the underlying nonequilibrium mechanism of perceptual rivalry and link thermodynamical results with neuroelectrophysiological experiments. Our framework provides a global and physical understanding of brain perception, which may go beyond cognitive science or psychology but embodies the connection with wider fields such as decision-making. Published by the American Physical Society 2025

Transformative Gamified Binocular Therapy for Unilateral Amblyopia in Young Children: Pilot Prospective Efficacy and Safety Study

Article

Jan 2025

Background Amblyopia is a common cause of visual impairment in children. Compliance with traditional treatments for amblyopia is challenging due to negative psychosocial impacts. Recent shifts in amblyopia treatment have moved from suppressing the dominant eye to enhancing binocular visual function. Binocular digital therapy has become a promising approach. Objective The aim of this study was to evaluate the effects of binocular gamified digital therapy on visual acuity and stereoacuity (SA) in children with unilateral amblyopia. Methods This pilot prospective study enrolled 11 children aged 4-6 years with unilateral amblyopia. Following at least 8 weeks of refractive correction, participants underwent binocular gamified digital therapy for 60 minutes per day, 5 days a week. The therapy used a roguelike shooting game delivered under binocular conditions through two independent channels with a real-time artificial intelligence visual engine. Assessments of distance visual acuity (DVA), near visual acuity (NVA), and SA were conducted at baseline and again at 4, 8, and 12 weeks. Results At 12 weeks, the following significant improvements were noted: amblyopic eye DVA improved by 1.0 line ( P =.01; d =0.77), binocular DVA improved by 0.7 lines ( P =.006; d =1.00), and SA improved by 0.3 logarithm (log) arcseconds ( P =.01; d =0.97). At 8 weeks, improvements included amblyopic eye DVA by 0.9 lines ( P =.046; d =1.00) and SA by 0.28 log arcseconds ( P =.02; d =0.90). No significant adverse events were observed, although one participant developed progressive esotropia. Conclusions Binocular gamified digital therapy is effective and safe for improving visual outcomes in children aged 4-6 years with unilateral amblyopia.

Brazilian best practice guidelines for amblyopia diagnosis and management

Article

Full-text available

Nov 2024

This study aimed to propose a guideline for amblyopia treatment and follow-up. Studies show that amblyopia leads to a series of perceptual deficits, including loss of visual acuity, stereoacuity, and contrast sensitivity. Perceptual changes are also found in the sound eye, such as those involving the types of motion perception. The gold standard of treatment remains the prescription of eyeglasses, when indicated, and patching of the dominant eye. The treatment is mostly effective in patients aged <7 years and must be discontinued gradually, tapering off patching for at least 5 weeks. Atropine may be performed for penalization in hyperopic children whose amblyopic eye has better visual acuity under cycloplegia than the fellow eye. The discovery of significant neural plasticity in the amblyopic brain after the critical period opens possibilities for new treatment modalities even after childhood. Keywords: Amblyopia; Atropine; Contrast sensitivity; Motion perception; Eyeglasses; Visual acuity; Prescriptions

Amblyopia rehabilitation: A preliminary study on the efficacy of an alternative therapeutic method within Italian patients

Article

Full-text available

Nov 2024

Introduction Amblyopia is the medical term for a “lazy eye.” It occurs when vision in one or both eyes does not develop properly during childhood even though there is no structural abnormality of the eye. It consists of an interocular difference of two lines or more in a visual acuity table (without specifying any), or visual acuity worse than or equal to 20/30 Snellen Feet equivalent to 0.2 LogMAR, with the best optical correction. (American Academy of Ophthalmology) Patching is the international gold standard amblyopia treatment, based on a monocular stimulation of the eye with lower vision. It needs high compliance and a long period of treatment during plastic age. The purpose of our work is to evaluate the efficiency of a different and faster method for amblyopia rehabilitation, useful even for patients out of the plastic age: specifically homebased binocular rehabilitation therapy through specific smartphone/tablet games combined with anagliphyc glasses. This method, due to its ease of use, high compliance and cheap cost, could reach a great number of patients that until now have the risk of being abandoned if they are not able, for different reason, to follow the others common therapies. Methods Fifty-five patients: mean age 8.98 ± 5.38, underwent ophthalmologic and orthoptic evaluations for amblyopia: BVCA with ETDRS logMAR, stereoacuity with Lang Stereotest I, ocular motility examination, fundus oculi and cycloplegic refraction examination. Eligible children had ⩾0.2 (as applicable) logMAR interocular difference, or BVCA worse or equal to 0.2 LogMAR. Patients were rehabilitated with specific dichoptic treatment by digital videogames for 1 hour/day for 2 months. Children wore red–blue anaglyphic glasses to play the games (with low-contrast components visible to 1 eye and high-contrast components visible to the other eye) for 7 hours per week (1 hour per day) for 8 weeks, with 2 outcome examinations programmed by protocol at 4 and 8 weeks from baseline. Results After 8 weeks of treatment, amblyopic eye BCVA improved from 0.28 ± 0.13 logMAR at baseline to 0.10 ± 0.09 (P < .05) logMAR, with an improvement of 0.18 ± 0.09 logMAR. Conclusion Achieved results relating to visual acuity improvements using binocular rehabilitation by digital videogames were statistically significant and encouraging. It is important that research and experimentation does not cease at this stage. Larger sample sizes, extended rehabilitation treatment periods and longer follow-up must be undertaken, in order to obtain objective data relating to visual acuity maintenance and also to obtained visual acuity results linked to age.

Binocular Imbalance Measured by SSVEP Predicts Impaired Stereoacuity in Amblyopia

Article

Full-text available

Oct 2024

Purpose The current study aims to implement steady-state visual evoked potentials (SSVEPs) in quantifying the binocular imbalance of amblyopia and to assess the predictive value of SSVEP-derived indices for amblyopic stereoacuity. Methods We measure frequency-tagged SSVEP responses elicited by each eye (F1 = 6 Hz through the fellow eye; F2 = 7.5 Hz through the amblyopic eye) within a binocular rivalry paradigm among a cohort of anisometropic amblyopic observers (n = 29, mean age: 12 years). Binocular suppression was quantified by assessing the disparity in SSVEP amplitudes between the eyes, while the strength of interocular interaction was evaluated through the intermodulation response at F1+F2 = 13.5 Hz. Subsequent analyses explored the associations between these neural indices and relevant behavioral metrics in amblyopia. Results Results reveal a significant difference in SSVEP amplitudes elicited from the fellow eye and the amblyopic eye, with the former exhibiting notably higher responses. Moreover, the fellow eye demonstrated prolonged dominance duration compared to its amblyopic counterpart. Furthermore, a negative correlation between binocular suppression and interocular interaction was observed, with stereoacuity showing a significant correlation with binocular suppression. Utilizing stepwise mulptiple linear regression analysis, we established that a predictive model combining binocular suppression and visual acuity of the amblyopic eye provided the best prediction of stereoacuity. Conclusions These results highlight the potential of binocular suppression, as assessed by SSVEPs within a binocular rivalry paradigm, as a promising neural predictor of stereopsis in amblyopia.

Nonequilibrium dynamics and thermodynamics provide the underlying physical mechanism of the perceptual rivalry

Preprint

Full-text available

Jun 2024

Perceptual rivalry, where conflicting sensory information leads to alternating perceptions crucial for associated cognitive function, has attracted researcher's attention for long. Despite progresses being made, recent studies have revealed limitations and inconsistencies in our understanding across various rivalry contexts. We develop a unified physical framework, where perception undergoes a consecutive phase transition process encompassing different multi-state competitions. We reveal the underlying mechanisms of perceptual rivalry by identifying dominant switching paths among perceptual states and quantifying mean perceptual durations, switching frequencies, and proportions of different perceptions. We uncover the underlying nonequilibrium dynamics and thermodynamics by analyzing average nonequilibrium flux and entropy production rate, while associated time series irreversibility reflects the underlying nonequilibrium mechanism of perceptual rivalry and link thermodynamical results with neuro-electrophysiological experiments. Our framework provides a global and physical understanding of brain perception, which may go beyond cognitive science or psychology but embodies the connection with wider fields as decision-making.

Peripheral Binocular Imbalance in Anisometropic and Strabismic Amblyopia

Article

Full-text available

Apr 2024

Purpose Individuals with amblyopia experience central vision deficits, including loss of visual acuity, binocular vision, and stereopsis. In this study, we examine the differences in peripheral binocular imbalance in children with anisometropic amblyopia, strabismic amblyopia, and typical binocular vision to determine if there are systematic patterns of deficits across the visual field. Methods This prospective cohort study recruited 12 participants with anisometropic amblyopia, 10 with strabismic amblyopia, and 10 typically sighted controls (age range, 5–18 years). Binocular imbalance was tested at 0°, 4°, and 8° eccentricities (4 angular locations each) using band-pass filtered Auckland optotypes (5 cycles per optotype) dichoptically presented with differing contrast to each eye. The interocular contrast ratio was adjusted until the participant reported each optotype with equal frequency. Results Participants with anisometropic and strabismic amblyopia had a more balanced contrast ratio, or decreased binocular imbalance, at 4° and 8° eccentricities as compared with central vision. Participants with strabismic amblyopia had significantly more binocular imbalance in the periphery as compared with individuals with anisometropic amblyopia or controls. A linear mixed effects model showed a main effect for strabismic amblyopia and eccentricity on binocular imbalance across the visual field. Conclusions There is evidence of decreased binocularity deficits, or interocular suppression, in the periphery in anisometropic and strabismic amblyopia as compared with controls. Notably, those with strabismic amblyopia exhibited more significant peripheral binocular imbalance. These variations in binocularity across the visual field among different amblyopia subtypes may necessitate tailored approaches for dichoptic treatment.

Dichoptic Game Training in Strabismic Amblyopia Improves the Visual Evoked Response

Article

Full-text available

Sep 2023

Dichoptic video gaming offers an alternative approach in amblyopia treatment by allowing different information to be presented in the two eyes, resulting to reduced suppression and/or enhanced fusion. The aim of this case report series is to evaluate the outcome of supervised dichoptic training, with the use of video games in a virtual reality (VR) system, on far and near visual acuity (VA), stereoacuity, and the visual evoked response of an adult and two children with strabismic amblyopia. Results suggest that despite the absence of improvement in VA following supervised dichoptic training, a remarkable increase in stereoacuity was evident with a concurrent decrease in phorias. Moreover, an improvement in the P100 latency of the pattern visual evoked potentials (VEPs) in the amblyopic eye was observed in all participants. Finally, at least two sessions per week were completed for each patient under continuous supervision, implying sufficient compliance and treatment efficiency with dichoptic video gaming. Supervised dichoptic training, consisting of at least 20 hours of video gaming using a VR system, improves stereoacuity and the latency of the visual evoked response in the amblyopic eye. This probably occurs by overcoming its suppression, indicating that the speed of visual processing, as evaluated by pattern VEPs, may precede improvements in VA.

Investigation of the efficacy and safety of retinal inactivation as a treatment for amblyopia in cats

Article

Full-text available

Jun 2023

Introduction Deprivation of normal vision early in postnatal development elicits modifications of neural circuitry within the primary visual pathway that can cause a severe and intractable vision impairment (amblyopia). In cats, amblyopia is often modeled with monocular deprivation (MD), a procedure that involves temporarily closing the lids of one eye. Following long-term MD, brief inactivation of the dominant eye’s retina can promote recovery from the anatomical and physiological effects of MD. In consideration of retinal inactivation as a viable treatment for amblyopia it is imperative to compare its efficacy against conventional therapy, as well as assess the safety of its administration. Methods In the current study we compared the respective efficacies of retinal inactivation and occlusion of the dominant eye (reverse occlusion) to elicit physiological recovery from a prior long-term MD in cats. Because deprivation of form vision has been associated with development of myopia, we also examined whether ocular axial length or refractive error were altered by a period of retinal inactivation. Results The results of this study demonstrate that after a period of MD, inactivation of the dominant eye for up to 10 days elicited significant recovery of visually-evoked potentials that was superior to the recovery measured after a comparable duration of reverse occlusion. After monocular retinal inactivation, measurements of ocular axial length and refractive error were not significantly altered from their pre-inactivation values. The rate of body weight gain also was not changed during the period of inactivation, indicating that general well-being was not affected. Discussion These results provide evidence that inactivation of the dominant eye after a period of amblyogenic rearing promotes better recovery than eye occlusion, and this recovery was achieved without development of form-deprivation myopia.

Comparison of a novel gamified binocular therapy and standard monocular patching therapy in treating unilateral amblyopia in young children: a prospective, multicenter, randomized controlled trial

Article

Full-text available

Jun 2025
TRIALS

Background Amblyopia is a leading cause of visual impairment in children, and conventional treatments often encounter challenges related to poor compliance and adverse psychosocial effects. Recent advancements in treatment approaches have evolved beyond merely suppressing the dominant eye, now focusing on improving binocular visual function. Binocular therapy has emerged as a promising and innovative approach. The study evaluates the efficacy of a novel gamified binocular therapy for treating unilateral amblyopia on comprehensive visual functions. Methods This prospective, multicenter, randomized, blinded, controlled trial is designed as a non-inferiority study. A total of 144 patients, aged 4 to 7 years, diagnosed with amblyopia, will be randomly assigned to either the intervention group (72 patients) or the control group (72 patients). Participants in the intervention group will engage in daily 1-h sessions of gamified binocular therapy, 5 days per week, for a total duration of 8 weeks (40 h). The treatment employs a roguelike shooting game, presented through binocular presentation via two distinct channels, powered by a real-time artificial intelligence-driven visual engine. The control group will receive traditional patching therapy for 2 h per day, 7 days per week for 8 weeks (112 h). The primary outcome measure of this study is distance visual acuity, while secondary outcome measures include stereoacuity and developmental visual perception assessed using the Developmental Test of Visual Perception (DTVP). These measures will be assessed at baseline and follow-up visits to determine the effectiveness of the intervention. Discussion This study is a multicenter randomized trial to evaluate the efficacy and safety of the Vision Planet Training System for the treatment of unilateral amblyopia in young children compared with standard monocular patching therapy. The results are anticipated to offer valuable insights into the efficacy of binocular treatment for unilateral amblyopia. Trial registration Chinese Clinical Trial Registry ChiCTR2300079090. Registered on 25 December 2023. https://www.chictr.org.cn/showproj.html?proj=215374.

Ocular Dominance Plasticity: A Mini-Review

Article

Full-text available

Jun 2025

Seung Hyun Min

Ocular dominance plasticity, the ability of the brain to change sensory eye balance, has traditionally been believed to be extremely limited in adult visual cortex. However, recent studies on short-term monocular deprivation (MD) demonstrate that its presence is prevalent in adult humans, as short-term MD is capable of significantly shifting ocular dominance in favor of the previously deprived eye. Thus, findings over the last 15 years highlight that short-term MD can be a promising alternative treatment for amblyopia, a neurodevelopmental disorder characterized by binocular imbalance. Conventionally, amblyopia has been treated with patching therapy, which shows limited effectiveness in restoring binocularity of adults and is associated with poor compliance rate and high psychosocial distress. Thus, it is an opportune time to explore how short-term MD can be utilized as an alternative treatment option for restoring amblyopic vision, especially individuals who do not respond robustly to standard treatment. This review provides an overview of foundational studies on ocular dominance plasticity in both visually intact and impaired observers. It also evaluates the potential of short-term MD as a treatment for amblyopia and suggests its future research directions, including the integration of multimodal therapeutic strategies that include short-term MD.

Hierarchical Bayesian augmented Hebbian reweighting model of perceptual learning

Article

Full-text available

Apr 2025
J VISION

The augmented Hebbian reweighting model (AHRM) has proven effective in modeling the collective performance of observers in perceptual learning studies. In this work, we introduce a novel hierarchical Bayesian version of the AHRM (HB-AHRM), which allows us to model the learning curves of individual participants and the entire population within a unified framework. We compare the performance of HB-AHRM with that of a Bayesian inference procedure, which independently estimates posterior distributions of model parameters for each participant without using a hierarchical structure. To address the substantial computational challenges, we propose a method for approximating the likelihood function in the AHRM through feature engineering and linear regression, increasing the speed of the estimation process by a factor of 20,000. This enhancement enables the HB-AHRM to compute the posterior distributions of hyperparameters and model parameters at the population, subject, and test levels, facilitating statistical inferences across these layers. Although developed in the context of a single experiment, the HB-AHRM and its associated methods are broadly applicable to data from various perceptual learning studies, offering predictions of human performance at both individual and population levels. Furthermore, the approximated likelihood approach may prove useful in fitting other stochastic models that lack analytic solutions.

Temporal Frequency Modulation of Binocular Balance in Normal and Amblyopic Vision

Article

Full-text available

Apr 2025

Purpose To investigate how temporal frequency modulates binocular balance in normally sighted and amblyopic adults. Methods Twenty-three controls and 13 amblyopes participated in this study. The effects of temporal frequency differences and monocularly directed attention on binocular balance were measured using an onset binocular rivalry task with sinusoidally flickering gratings at varying temporal frequencies and static gratings with monocular attentional cues. For the flickering gratings, different combinations of temporal frequencies (2, 4, or 10 Hz in one eye vs. 2, 3, 4, 6, 10, 15, or 20 Hz in the other) were presented. Their effects were then compared, and their relationship was analyzed. Results There was no relationship between the shifts in balance from temporal frequency and monocularly directed attention in both controls and amblyopes. Intermediate temporal frequencies (8.9 ± 1.4 Hz) in one eye maximized its perceptual dominance, with a larger shift due to temporal frequency in amblyopes than in controls. While normally sighted observers experienced similar degrees of shift in balance from temporal frequency and attentional (active and passive) modulations, amblyopic observers experienced a larger shift from temporal frequency than from monocularly focused passive (but not active) attention. Conclusions Intermediate temporal frequencies in one eye, rather than a specific temporal frequency difference between both eyes, maximized its perceptual dominance in both normally sighted and amblyopic observers. This balance shift from temporal frequency modulation was larger in amblyopes than in controls. Finally, the effect of temporal frequency on balance was larger than that of monocularly directed passive attention in amblyopes.

Fixation Stability Deficits in Anisometropic Amblyopia

Article

Full-text available

Jan 2025

Purpose The purpose of this study was to investigate the relationship between fixation stability deficits in anisometropic amblyopia and various visual functions, as well as the underlying retinal structure. Methods All 164 patients with anisometropic amblyopia were recruited in this cross-sectional study. The contrast sensitivity function (CSF) was measured using the qCSF method, whereas the MP-3 microperimeter was used to assess fixation stability and locate the preferred retinal locus. Bivariate contour ellipse area (BCEA) of both the amblyopic and the fellow eyes was used as the dependent variable. Based on previous research and clinical practice, the following variables were selected as independent variables for regression modeling to explore potential influencing factors: gender, age, area under the log CSF (AULCSF), absolute interocular difference (IOD) in spherical equivalent refraction (SER), AULCSF-IOD, the eccentricity of the preferred retinal locus, patching history, and the log BCEA of the contralateral eye. Results A total of 161 participants (87 men and 74 women, average age = 20.26 ± 8.79 years, ranging from 5 to 51 years old) completed all examinations. Three participants were excluded due to their inability to complete the required examinations. There were significant differences between the amblyopic and the fellow eyes in terms of SER, best-corrected visual acuity, AULCSF, log BCEA, and the eccentricity of the preferred retinal locus (all P < 0.001). Both the amblyopic and the fellow eyes exhibited fixation stability deficits and eccentric fixation. The regression model showed that fixation stability in the amblyopic eye (log BCEA) was significantly associated with age, AULCSF of the amblyopic eye, AULCSF-IOD, eccentricity of the amblyopic eye, and log BCEA of the fellow eye (all P < 0.05). Fixation stability in the fellow eye (log BCEA) was significantly associated with eccentricity of the fellow eye, and log BCEA of the amblyopic eye (all P < 0.05). Conclusions Eccentric fixation and fixation stability deficits were observed in both the amblyopic and the fellow eyes, with fixation stability in both eyes being correlated with the eccentricity of the preferred retinal locus. These findings suggest that in the clinical management of amblyopia, attention should be given to the fixation stability and fixation characteristics of both the amblyopic and fellow eyes.

Significance of binocular fusion in enhancing visual acuity during amblyopia treatment

Article

Full-text available

Oct 2024

Background: Currently, the exploration of amblyopia treatment methods is gradually shifting to the restoration of binocular visual perceptual function. Binocular fusion function, as an important component of binocular visual function, mainly reflects the patient's ability to integrate the signals received from both eyes. In this study, we investigated the relationship between binocular fusion function and improvement in visual acuity during amblyopia treatment. Methods: A retrospective analysis was conducted on a cohort of patients with amblyopia, aged 3-14 years old, who visited an outpatient clinic in Shenzhen Eye Hospital between May 2021 and January 2023. The investigation included 105 patients (210 eyes) with isometropic or anisometropic amblyopia. All participants underwent cycloplegic refraction examination and binocular fusion function measurement. All patients underwent standard amblyopia treatment, and those with the best-corrected visual acuity (BCVA) of 0.6 or higher in the amblyopic eye of both eyes received binocular fusion training using a computer platform. Results: A statistically significant negative correlation (-0.263, P=0.007) was observed between the absolute difference in binocular BCVA and binocular fusion function at the start of treatment (baseline). Linear regression analysis revealed that the improvement in BCVA in the amblyopic eye exhibited correlations with several factors, including the baseline binocular BCVA difference, baseline BCVA of the amblyopic eye, improvement in binocular fusion function, and the number of fusion training sessions (regression coefficients: -0.463, -0.771, 0.007, and 0.063, respectively; all P<0.05). Two patterns of binocular fusion function development during treatment were identified using group-based trajectory modeling (GBTM): the slow growth pattern and the rapid growth pattern. The results of a multivariate logistic regression model indicated a statistically significant link between fusion training and the development pattern of binocular fusion function [odds ratio (OR): 5.219, 95% confidence interval (CI): 2.045-13.323]. Conclusions: Enhancing binocular fusion function may result in an improvement of BCVA in the amblyopic eye of patients with amblyopia. The frequency of binocular fusion training is crucial for rapid improvement in binocular fusion function.

Visual Performance of Children with Amblyopia after 6 Weeks of Home-Based Dichoptic Visual Training

Article

Full-text available

Aug 2024

Objectives: This study was aimed at analyzing the efficacy on the improvement of the visual function of a dichoptic online cloud-based platform for the treatment of amblyopia in anisometropic children. Methods: A quasi-experimental (pretest–post-test) study was conducted in 23 subjects with ages from 5 to 15 years old with anisometropic amblyopia combined with additional presence (2 subjects) or not (21 subjects) of microtropia. A total of 30 home-based training sessions of 30 min per session with Bynocs® platform were prescribed for 6 weeks. Results: Amblyopic eye logMAR visual acuity (VA) significantly improved from 0.28 ± 0.24 to 0.13 ± 0.20 after the 6-week treatment (p < 0.001). At baseline, 60.9% of participants had VA in amblyopic eye of 0.20 logMAR or worse, whereas this percentage decreased to 21.7% after treatment. Binocular function (BF) significantly improved from 2.82 ± 1.11 to 2.32 ± 0.94 (p < 0.001). Mean compliance was 92%, 87% and 93% at 2, 4 and 6 weeks of treatment, respectively. Conclusions: In conclusion, home-based dichoptic training with the digital platform evaluated is an effective method to improve amblyopic VA and stereoacuity in children with anisometropic amblyopia combined or not with microtropia.

Rehabilitation of amblyopia using a digital platform for visual training combined with patching in children: a prospective study

Article

Full-text available

Apr 2024
GRAEF ARCH CLIN EXP

Purpose To assess the possible benefits of the use of perceptual learning and dichoptic therapy combined with patching in children with amblyopia over the use of only patching. Methods Quasi-experimental multicentric study including 52 amblyopic children. Patients who improved their visual acuity (VA) by combining spectacles and patching were included in patching group (PG: 20 subjects), whereas those that did not improved with patching performed visual training (perceptual learning + dichoptic therapy) combined with patching, being assigned to the visual treatment group (VT: 32 subjects). Changes in VA, contrast sensitivity (CS), and stereopsis were monitored during a 6-month follow-up in each group. Results Significant improvements in VA were found in both groups at 1 month (p < 0.01). The total improvement of VA was 0.18 ± 0.16 and 0.31 ± 0.35 logMAR in PG and VT groups, respectively (p = 0.317). The Wilcoxon effect size was slightly higher in VT (0.48 vs. 0.54) at 6 months. An enhancement in CS was observed in the amblyopic eye of the VT group for all spatial frequencies at 1 month (p < 0.001). Likewise, the binocular function score also increased significantly in VT group (p = 0.002). A prediction equation of VA improvement at 1 month in VT group was obtained by multiple linear regression analysis (p < 0.001, R² = 0.747). Conclusions A combined treatment of visual training and patching is effective for obtaining a predictable improvement of VA, CS, and binocularity in patching-resistant amblyopic children.

Motion-Defined Form Perception in Deprivation Amblyopia

Article

Full-text available

Apr 2024

Purpose: The purpose of this study was to assess motion-defined form perception, including the association with clinical and sensory factors that may drive performance, in each eye of children with deprivation amblyopia due to unilateral cataract. Methods: Coherence thresholds for orientation discrimination of motion-defined form were measured using a staircase procedure in 30 children with deprivation amblyopia and 59 age-matched controls. Visual acuity, stereoacuity, fusion, and interocular suppression were also measured. Fixation stability and fellow-eye global motion thresholds were measured in a subset of children. Results: Motion-defined form coherence thresholds were elevated in 90% of children with deprivation amblyopia when viewing with the amblyopic eye and in 40% when viewing with the fellow eye. The deficit was similar in children with a cataract that had been visually significant at birth (congenital) and in children for whom the cataract appeared later in infancy or childhood (developmental). Poorer motion-defined form perception in amblyopic eyes was associated with poorer visual acuity, poorer binocular function, greater interocular suppression, and the presence of nystagmus. Fellow-eye deficits were not associated with any of these factors, but a temporo-nasal asymmetry for global motion perception in favor of nasalward motion suggested a general disruption in motion perception. Conclusions: Deficits in motion-defined form perception are common in children with deprivation amblyopia and may reflect a problem in motion processing that relies on binocular mechanisms.

Associations between the cause of amblyopia and pre-treatment contrast sensitivity, stereoacuity, fixation, and nystagmus

Article

Full-text available

Mar 2024

Purpose To explore the association between the cause of amblyopia and pre-treatment contrast sensitivity, stereoacuity, fixation and nystagmus. Design Retrospective cohort study. Methods A retrospective review was conducted for 3408 patients with amblyopia who had not yet started amblyopia treatment utilizing a large amblyopia patient database maintained at Zhongshan Ophthalmic Centre. Six amblyogenic factor subtypes were identified: anisometropia, isoametropia, strabismus, anisometropia and strabismus, monocular visual deprivation, and binocular visual deprivation amblyopia. Monocular best corrected visual acuity (BCVA), the contrast sensitivity function (CSF), fixation, and stereopsis were compared between the subtypes before and after propensity score matching (PSM) for age and sex. Results The two deprivation groups had poorer BCVA and CSF than the other groups. There were no systematic differences in CSF between the non-deprivation groups. Nystagmus was more common in the bilateral amblyopia groups compared to the monocular amblyopia groups. Eccentric fixation was uncommon with the exception of the anisometropia and strabismus group which had an eccentric fixation rate of 20%. Distance stereoacuity measured without monocular cues was absent for almost all patients. The results were consistent when analyzed using PSM. Conclusion Visual deprivation causes more severe amblyopia than other amblyogenic factors. For non-deprivation amblyopia subtypes, individual differences such as variation in the severity of the amblyogenic factor might be more important in determining pre-treatment vision than whether amblyopia was caused by refractive error, strabismus or both.

Amblyopia—A novel virtual round table to explore the caregiver perspective

Article

Full-text available

Jul 2023
OPHTHAL PHYSL OPT

Purpose A survey aimed to capture the caregiver's perspective on the impact of amblyopia and its treatment on the child and family, as well as caregivers' views on the design and feasibility of clinical trials investigating dichoptic binocular therapies for amblyopia. Methods Parents of amblyopic children, patient advocates and healthcare professionals took part in a moderated, structured discussion on a novel virtual advisory‐board platform. Results Seven parents of children with amblyopia, two patient organisation representatives, one ophthalmologist and one optometrist participated in the survey. A total of 645 posts were entered on the platform over a 14‐day period in September 2021. There was widespread agreement that the management of amblyopia poses more of a burden on the child and family than the condition itself, with treatment burden accentuated when treatment is unsuccessful. Parents expressed uncertainty and frustration in relation to the duration of patching, success of patching and alternative treatment options, and felt there was inadequate readily available, easy‐to‐understand information on the condition. Parents reported that a new treatment for amblyopia, such as dichoptic binocular therapy using video games, should be safe, non‐invasive and engaging compared with an eye patch. Treating at home, potentially for a shorter treatment duration, and with an entertaining game were the main reasons parents would join a clinical study with this type of novel therapy. However, due to a limited critical period treatment window, parents would feel more comfortable joining a clinical trial if traditional therapies were offered in conjunction with those under investigation. Conclusion Patient perspectives and the role of caregivers in the acceptance of any interventional treatments are increasingly recognised. Understanding how amblyopia and its treatment impacts a child and family should be an important premise to guide therapy and evaluate treatment value, both in clinical trials and in routine medical practice.

Amblyopia management

Article

Jul 2023

Characteristics and predictive factors of visual function improvements after monocular perceptual learning in amblyopia

Article

Full-text available

Jun 2023

Monocular perceptual learning has shown promising performance in restoring visual function in amblyopes beyond the critical period in the laboratory. However, the treatment outcome is variable and indeterminate in actual clinical and neuroscientific practice. We aimed to explore the efficacy of monocular perceptual learning in the clinical setting. By combining continuous monitoring of perceptual learning and clinical measurements, we evaluated the efficacy and characteristics of visual acuity and contrast sensitivity function improvement and further explored the individualized effect after perceptual learning. Amblyopes (average age:17 ± 7 years old) were trained in a monocular two-alternative forced choice identification task at the 50% contrast threshold of the amblyopic eye for 10–15 days. We found that monocular perceptual learning improves both visual acuity and contrast sensitivity function in amblyopia. The broader activation of spatial contrast sensitivity, with a significant improvement in lower spatial frequencies, contributed to improving visual acuity. Visual acuity changes in the early stage can predict the endpoint treatment outcomes. Our results confirm the efficacy of monocular perceptual learning and suggest potential predictors of training outcomes to assist in the future management of clinical intervention and vision neuroscience research in amblyopia beyond the critical period of visual plasticity.

Amblyopia Treatment through Immersive Virtual Reality: A Preliminary Experience in Anisometropic Children

Article

Full-text available

May 2023

The use of digital devices provides a wide range of possibilities for measuring and improving visual function, including concepts such as perceptual learning and dichoptic therapy. Different technologies can be used to apply these concepts, including, in recent years, the introduction of virtual reality (VR) systems. A preliminary experience in treating anisometropic amblyopia through an immersive VR device and using prototype software is described. A total of 4 children were treated by performing 18 office-based sessions. Results showed that distance VA in amblyopic eyes remained constant in two subjects, whereas the younger subjects improved after the training. Near VA improved in three subjects. All subjects showed an increase in the stereopsis of at least one step, with three subjects showing a final stereopsis of a 60 s arc. A total of three subjects showed an increase of approximately 0.5 CS units for the spatial frequency of 3 cpd after the training. Results from this pilot study suggest that visual training based on perceptual learning through an immersive VR environment could be a viable treatment for improving CS, VA, and stereopsis in some children with anisometropic amblyopia. Future studies should support these preliminary results.

Advances in artificial intelligence models and algorithms in the field of optometry

Article

Full-text available

Apr 2023

The rapid development of computer science over the past few decades has led to unprecedented progress in the field of artificial intelligence (AI). Its wide application in ophthalmology, especially image processing and data analysis, is particularly extensive and its performance excellent. In recent years, AI has been increasingly applied in optometry with remarkable results. This review is a summary of the application progress of different AI models and algorithms used in optometry (for problems such as myopia, strabismus, amblyopia, keratoconus, and intraocular lens) and includes a discussion of the limitations and challenges associated with its application in this field.

Quantitative evaluation of anisometropic amblyopia treatment efficacy by coupling multiple visual functions via CRITIC algorithm

Article

Full-text available

Apr 2023
BMC Ophthalmol

Background The evaluation of amblyopia treatment efficacy is essential for amblyopia prevention, control, and rehabilitation. Methods To evaluate the amblyopia treatment efficacy more precisely and quantitatively, this study recorded four visual function examination results, i.e., visual acuity, binocular rivalry balance point, perceptual eye position, and stereopsis before and after amblyopia treatment. Results We found that all these four results had a significant difference between before and after treatment, and the relationship between visual acuity improvement and the difference of BRBP, PEP, and stereoacuity cannot show a fitting correlation regarding the widely used index of visual acuity as the standard of treatment efficacy. By using the Criteria Importance Through Inter-criteria Correlation (CRITIC) method, a more comprehensive and quantitative index by coupling the selected four indexes with objective weights was obtained for further training efficacy representation, and the validation dataset also showed a good performance. Conclusions This study proved that our proposed coupling method based on different visual function examination results via the CRITIC algorithm is a potential means to quantify the amblyopia treatment efficacy.

Do monocular myopia children need to wear glasses? Effects of monocular myopia on visual function and binocular balance

Article

Full-text available

Mar 2023

Objective This study aims to compare the binocular visual functions and balance among monocular myopic adolescents and adults and binocular low myopic adolescents and explore whether monocular myopia requires glasses. Methods A total of 106 patients participated in this study. All patients were divided into three groups: the monocular myopia children group (Group 1 = 41 patients), the monocular myopia adult group (Group 2 = 26 patients) and the binocular low myopia children group (Group 3 = 39 patients). The refractive parameters, accommodation, stereopsis, and binocular balance were compared. Results The binocular refractive difference in Group 1, Group 2, and Group 3 was −1.37 ± 0.93, −1.94 ± 0.91, and −0.32 ± 0.27 D, respectively. Moreover, uncorrected visual acuity (UCVA), spherical equivalent (SE) and monocular accommodative amplitude (AA) between myopic and emmetropic eyes in Group 1 and Group 2 were significantly different (all P < 0.05). There was a significant difference in the accommodative facility (AF) between myopic and emmetropic eyes in Group 2 (t = 2.131, P = 0.043). Furthermore, significant differences were found in monocular AA (t = 6.879, P < 0.001), binocular AA (t = 5.043, P < 0.001) and binocular AF (t = −3.074, P = 0.003) between Group 1 and Group 2. The normal ratio of stereopsis according to the random dots test in Group 1 was higher than in Group 2 (χ2 = 14.596, P < 0.001). The normal ratio of dynamic stereopsis in Group 1 was lower than in Group 3 (χ2 = 13.281, P < 0.001). The normal signal-to-noise ratio of the binocular balance point in Group 1 was lower than Group 3 (χ2 = 4.755, P = 0.029). Conclusion First, monocular myopia could lead to accommodative dysfunction and unbalanced input of binocular visual signals, resulting in myopia progression. Second, monocular myopia may also be accompanied by stereopsis dysfunction, and long-term uncorrected monocular myopia may worsen stereopsis acuity in adulthood. In addition, patients with monocular myopia could exhibit stereopsis dysfunction at an early stage. Therefore, children with monocular myopia must wear glasses to restore binocular balance and visual functions, thereby delaying myopia progression.

METHODS OF AMBLYOPIA TREATMENT

Article

Jan 2023

A systematic review: Virtual-reality-based techniques for human exercises and health improvement

Article

Full-text available

Mar 2023

Virtual Reality (VR) has emerged as a new safe and efficient tool for the rehabilitation of many childhood and adulthood illnesses. VR-based therapies have the potential to improve both motor and functional skills in a wide range of age groups through cortical reorganization and the activation of various neuronal connections. Recently, the potential for using serious VR-based games that combine perceptual learning and dichoptic stimulation has been explored for the rehabilitation of ophthalmological and neurological disorders. In ophthalmology, several clinical studies have demonstrated the ability to use VR training to enhance stereopsis, contrast sensitivity, and visual acuity. The use of VR technology provides a significant advantage in training each eye individually without requiring occlusion or penalty. In neurological disorders, the majority of patients undergo recurrent episodes (relapses) of neurological impairment, however, in a few cases (60–80%), the illness progresses over time and becomes chronic, consequential in cumulated motor disability and cognitive deficits. Current research on memory restoration has been spurred by theories about brain plasticity and findings concerning the nervous system's capacity to reconstruct cellular synapses as a result of interaction with enriched environments. Therefore, the use of VR training can play an important role in the improvement of cognitive function and motor disability. Although there are several reviews in the community employing relevant Artificial Intelligence in healthcare, VR has not yet been thoroughly examined in this regard. In this systematic review, we examine the key ideas of VR-based training for prevention and control measurements in ocular diseases such as Myopia, Amblyopia, Presbyopia, and Age-related Macular Degeneration (AMD), and neurological disorders such as Alzheimer, Multiple Sclerosis (MS) Epilepsy and Autism spectrum disorder. This review highlights the fundamentals of VR technologies regarding their clinical research in healthcare. Moreover, these findings will raise community awareness of using VR training and help researchers to learn new techniques to prevent and cure different diseases. We further discuss the current challenges of using VR devices, as well as the future prospects of human training.

The Use of Vision Therapy in the Treatment of Refractory Amblyopia

Chapter

Jun 2025

Daniel Ledwoń

Novel Device for Intraoperative Quantitative Measurements of Extraocular Muscle Tensile Strength

Article

May 2025

Understanding the tensile properties of extraocular muscles (EOMs) is crucial for successful strabismus surgery and accurate predictions of surgical outcomes. Assessments of EOM tensile strength are traditionally highly dependent on the expertise of the ophthalmic surgeon, since they involve manually pulling the EOM in opposite directions. This approach only provides subjective measurements that are not quantifiable. Previous quantitative approaches have utilized various devices such as implanted force transducers or dial tension gauges connected to muscle tendons with nylon sutures, but these methods are complex and so are rarely used outside of research settings. Consequently, the goal of this study was to create a quantitative and clinically applicable device for assessing EOM tensile strength. This developed device uses a strabismus hook connected to a strain gauge load cell that measures the tensile force and includes a tilting sensor to ensure that the hook is pulled at a consistent angle when a force is applied. The performance of the device was tested on 22 EOMs in 11 patients with intermittent exotropia during surgery for resecting the medial rectus (MR) and recessing the lateral rectus (LR) under general anesthesia. The measured tensile strengths of the MR and LR were 284.9 ± 58.3 and 278.3 ± 64.6 g (mean ± SD), respectively. In conclusion, the novel device developed in this study for quantitative measurements of EOM tensile strength in clinical settings will facilitate understanding of the pathophysiology of strabismus, as well as of the mechanical properties of the EOMs, and enhance the precision of surgical interventions.

An Extensible Open Source Software Designed for Virtual Reality-based Testing and Treatment of Vision Disorders

Article

May 2025
ACM T APPL PERCEPT

Large-scale screening programs for vision impairments can incur substantial costs. Computer-based screening methods, which combine different measurements within a single system, can facilitate and reduce the costs of such programs. Here, we present a virtual reality (VR) software, which includes tests for the assessment of visual acuity, stereo acuity, eye misalignments and interocular suppression as well as games targeting different visual functions that may serve as treatment methods. The software can be easily extended to incorporate new tests and games. We present a proof of concept demonstrating the functionality of the software and its applicability in individuals with impaired binocularity. We evaluate a stereoacuity test in VR based on disparity detection using contoured objects by comparing its results to those obtained by standard clinical tests, i.e. TNO, Randot and Titmus, for 7 amblyopes and 6 healthy controls. We evaluate the applicability of a new VR-based suppression test in 10 amblyopes and 6 healthy individuals. For the latter we exploit the effects of short-term monocular deprivation, which induce a change of ocular dominance. Finally, we outline technical limitations and discuss potential applications.

Functional consequences of amblyopia and its impact on health-related quality of life

Article

May 2025

Attention deficits in Amblyopia: A narrative review

Article

Apr 2025

Is dichoptic a new era of amblyopia treatment?

Article

Jan 2025
J AAPOS

Steven M. Archer

Amblyopie

Article

Apr 2020

Christophe Orssaud

Real-World Evidence on Digital Therapeutics in Pediatric Amblyopia: Insights into Rapid Axial Elongation Risk

Article

Jan 2025
OPHTHALMOLOGY

Cost Effectiveness Analysis of Digital Therapeutics for Amblyopia

Article

Jan 2025
OPHTHALMOLOGY

Amblyopic binocular imbalance quantified by the dichoptic contrast ordering test and dichoptic letters test

Article

Full-text available

Jan 2025

In amblyopia, abnormal binocular interactions lead to an overwhelming dominance of one eye. One mechanism implied in this imbalance is the suppression between the inputs from the two eyes. This interocular suppression involves two components: an overlay suppression and a surround suppression. Here, we propose a new method for measuring surround suppression which has been demonstrated in both strabismic and anisometropic amblyopes, based on a novel interocular contrast scaling task, suitable for use as a clinical tool. We compare the results obtained with this method against those from another method designed to measure overlay suppression: the Dichoptic Letter Test. We find a strong correlation between the results obtained with the two methods. Additionally, we observe strong correlations between the imbalance measured with the two tests and visual acuity and stereopsis. Altogether this suggests that amblyopic suppression is spatially broad and has direct relevance in global vision. So our new method is a relevant, clinically suitable tool to track the disease state in amblyopia.

Hierarchical Bayesian Augmented Hebbian Reweighting Model of Perceptual Learning

Preprint

Full-text available

Aug 2024

The Augmented Hebbian Reweighting Model (AHRM) has been effectively utilized to model the collective performance of observers in various perceptual learning studies. In this work, we have introduced a novel hierarchical Bayesian Augmented Hebbian Reweighting Model (HB-AHRM) to simultaneously model the learning curves of individual participants and the entire population within a single framework. We have compared its performance to that of a Bayesian Inference Procedure (BIP), which independently estimates the posterior distributions of model parameters for each individual subject without employing a hierarchical structure. To cope with the substantial computational demands, we developed an approach to approximate the likelihood function in the AHRM with feature engineering and linear regression, increasing the speed of the estimation procedure by 20,000 times. The HB-AHRM has enabled us to compute the joint posterior distribution of hyperparameters and parameters at the population, observer, and test levels, facilitating statistical inferences across these levels. While we have developed this methodology within the context of a single experiment, the HB-AHRM and the associated modeling techniques can be readily applied to analyze data from various perceptual learning experiments and provide predictions of human performance at both the population and individual levels. The likelihood approximation concept introduced in this study may have broader utility in fitting other stochastic models lacking analytic forms.

Application of electrostimulation and magnetic stimulation in patients with optic neuropathy: A mechanistic review

Article

Jun 2024
DEV NEUROBIOL

Visual impairment caused by optic neuropathies is irreversible because retinal ganglion cells (RGCs), the specialized neurons of the retina, do not have the capacity for self-renewal and self-repair. Blindness caused by optic nerve neuropathies causes extensive physical, financial, and social consequences in human societies. Recent studies on different animal models and humans have established effective strategies to prevent further RGC degeneration and replace the cells that have deteriorated. In this review, we discuss the application of electrical stimulation (ES) and magnetic field stimulation (MFS) in optic neuropathies, their mechanisms of action, their advantages, and limitations. ES and MFS can be applied effectively in the field of neuroregeneration.. Although stem cells are becoming a promising approach for regenerating RGCs, the inhibitory environment of the CNS and the long visual pathway from the optic nerve to the superior colliculus are critical barriers to overcome. Scientific evidence has shown that adjuvant treatments, such as the application of ES and MFS help direct thetransplanted RGCs to extend their axons and form new synapses in the central nervous system (CNS). In addition, these techniques improve CNS neuroplasticity and decrease the inhibitory effects of the CNS. Possible mechanisms mediating the effects of electrical current on biological tissues include the release of anti-inflammatory cytokines, improvement of microcirculation, stimulation of cell metabolism, and modification of stem cell function. ES and MFS have the potential to promote angiogenesis, direct axon growth toward the intended target, and enhance appropriate synaptogenesis in optic nerve regeneration.

Leveraging neural plasticity for the treatment of amblyopia

Article

May 2024

Flash Suppression Reveals an Additional Nonvisual Extrastriate Contribution for Amblyopic Suppression

Article

Feb 2024

Purpose A growing body of evidence suggests that anomalous binocular interactions underlie the deficits in amblyopia, but their nature and neural basis are still not fully understood. Methods We examined the behavioral and neural correlates of interocular suppression in 13 adult amblyopes and 13 matched controls using a flash suppression paradigm while recording steady-state visual evoked potentials. The strength of suppression was manipulated by changing the contrast (10%, 20%, 30%, or 100%) of the flash stimulus, or the suppressor, presented either in the dominant (fellow) or nondominant (amblyopic) eye. Results At the behavioral level, interocular suppression in normal observers was found, regardless of the eye origin of the flash onset. However, the pattern of suppression in the amblyopes was not symmetric, meaning that the suppression from the dominant eye was stronger, supporting a putative chronic suppression of the amblyopic eye. Interestingly, the amblyopic eye was able to suppress the dominant eye but only at the highest contrast level. At the electrophysiology level, suppression of the steady-state visual evoked potential responses in both groups in all conditions was similar over the occipital region, but differed over the frontal region. Conclusions Our findings suggest that, although suppression in amblyopia involves an imbalanced interaction between the inputs to the two eyes in the visual cortex, there is also involvement of nonvisual extrastriate areas.

Daily dose–response from short‐term monocular deprivation in adult humans

Article

Full-text available

Feb 2024
OPHTHAL PHYSL OPT

Short‐term monocular deprivation (MD) shifts sensory eye balance in favour of the previously deprived eye. The effect of MD on eye balance is significant but brief in adult humans. Recently, researchers and clinicians have attempted to implement MD in clinical settings for adults with impaired binocular vision. Although the effect of MD has been studied in detail in single‐session protocols, what is not known is whether the effect of MD on eye balance deteriorates after repeated periods of MD (termed ‘perceptual deterioration’). An answer to this question is relevant for two reasons. Firstly, the effect of MD (i.e., dose‐response) should not decrease with repeated use if MD is to be used therapeutically (e.g., daily for weeks). Second, it bears upon the question of whether the neural basis of the effects of MD and contrast adaptation, a closely related phenomenon, is the same. The sensory change from contrast adaptation depends on recent experience. If the observer has recently experienced the same adaptation multiple times for consecutive days, then the adaptation effect will be smaller because contrast adaptation exhibits perceptual deterioration, so it is of interest to know if the effects of MD follow suit. This study measured the effect of 2‐h MD for seven consecutive days on binocular balance of 15 normally sighted adults. We found that the shift in eye balance from MD stayed consistent, showing no signs of deterioration after subjects experienced multiple periods of MD. This finding shows no loss of effectiveness of repeated daily doses of MD if used therapeutically to rebalance binocular vision in otherwise normal individuals. Furthermore, ocular dominance plasticity, which is the basis of the effects of short‐term MD, does not seem to share the property of ‘perceptual deterioration’ with contrast adaptation, suggesting different neural bases for these two related phenomena.

Managing Pediatric Cataract Patients: Amblyopia Treatment and Binocularity Outcomes

Article

Nov 2023

Wanda Pfeifer

Can artificial intelligence be used to improve the quality of vision in patients with amblyopia? The first digital pill in medicine administered under AI

Article

Aug 2023

Amblyopic stereo vision is efficient but noisy

Article

Jun 2023

People with amblyopia demonstrate a reduced ability to judge depth using stereopsis. Our understanding of this deficit is limited, as standard clinical stereo tests may not be suited to give a quantitative account of the residual stereo ability in amblyopia. In this study we used a stereo test designed specifically for that purpose. Participants identified the location of a disparity-defined odd-one-out target within a random-dot display. We tested 29 amblyopic (3 strabismic, 17 anisometropic, 9 mixed) participants and 17 control participants. We obtained stereoacuity thresholds from 59% of our amblyopic participants. There was a factor of two difference between the median stereoacuity of our amblyopic (103 arcsec) and control (56 arcsec) groups. We used the equivalent noise method to evaluate the role of equivalent internal noise and processing efficiency in amblyopic stereopsis. Using the linear amplifier model (LAM), we determined the threshold difference was due to a greater equivalent internal noise in the amblyopic group (238 vs 135 arcsec), with no significant difference in processing efficiency. A multiple linear regression determined 56% of the stereoacuity variance within the amblyopic group was predicted by the two LAM parameters, with equivalent internal noise predicting 46% alone. Analysis of control group data aligned with our previous work, finding that trade-offs between equivalent internal noise and efficiency play a greater role. Our results allow a better understanding of what is limiting amblyopic performance in our task. We find this to be a reduced quality of disparity signals in the input to the task-specific processing.

Perceptual learning based on a temporal stimulus enhances visual function in adult amblyopic subjects

Article

Full-text available

May 2023

Studies have shown that Perceptual Learning (PL) can lead to enhancement of spatial visual functions in amblyopic subjects. Here we aimed to determine whether a simple flickering stimulus can be utilized in PL to enhance temporal function performance and whether enhancement will transfer to spatial functions in amblyopic subjects. Six adult amblyopic and six normally sighted subjects underwent an evaluation of their performance of baseline psychophysics spatial functions (Visual acuity (VA), contrast sensitivity (CS), temporal functions (critical fusion frequency (CFF) test), as well as a static and flickering stereopsis test, and an electrophysiological evaluation (VEP). The subjects then underwent 5 training sessions (on average, a total of 150 min over 2.5 weeks), which included a task similar to the CFF test using the method of constant stimuli. After completing the training sessions, subjects repeated the initial performance evaluation tasks. All amblyopic subjects showed improved temporal visual performance (CFF) in the amblyopic eye (on average, 17%, p << 0.01) following temporal PL. Generalization to spatial, spatio-temporal, and binocular tasks was also found: VA increased by 0.12 logMAR (p = 0.004), CS in backward masking significantly increased (by up to 19%, p = 0.003), and flickering stereopsis increased by 85 arcsec (p = 0.048). These results were further electrophysiologically manifested by an increase in VEP amplitude (by 43%, p = 0.03), increased Signal-to-Noise ratio (SNR) (by 39%, p = 0.024) to levels not different from normally sighted subjects, along with an improvement in inter-ocular delay (by 5.8 ms, p = 0.003). In contrast, no significant effect of training was found in the normally sighted group. These results highlight the potential of PL based on a temporal stimulus to improve the temporal and spatial visual performance in amblyopes. Future work is needed to optimize this method for clinical applications.

Binocular vision

Chapter

Jan 2017

Theory for the development of neuron selectivity: orientation specificity and binocular interaction in visual cortex

Article

Full-text available

Jan 1982

The development of stimulus selectivity in the primary sensory cortex of higher vertebrates is considered in a general mathematical framework. A synaptic evolution scheme of a new kind is proposed in which incoming patterns rather than converging afferents compete. The change in the efficacy of a given synapse depends not only on instantaneous pre- and postsynaptic activities but also on a slowly varying time-averaged value of the postsynaptic activity. Assuming an appropriate nonlinear form for this dependence, development of selectivity is obtained under quite general conditions on the sensory environment. One does not require nonlinearity of the neuron's integrative power nor does one need to assume any particular form for intracortical circuitry. This is first illustrated in simple cases, e.g., when the environment consists of only two different stimuli presented alternately in a random manner. The following formal statement then holds: the state of the system converges with probability 1 to points of maximum selectivity in the state space. We next consider the problem of early development of orientation selectivity and binocular interaction in primary visual cortex. Giving the environment an appropriate form, we obtain orientation tuning curves and ocular dominance comparable to what is observed in normally reared adult cats or monkeys. Simulations with binocular input and various types of normal or altered environments show good agreement with the relevant experimental data. Experiments are suggested that could test our theory further.

[Non-invasive brain stimulation]

Article

Full-text available

Oct 2015
NERVENARZT

Comparing dichoptic action video game play to patching in adults with amblyopia.

Poster

Full-text available

Aug 2014
J VISION

Adults with amblyopia, a condition characterized by reduced visual acuity (VA) and stereopsis, may benefit from playing action video games with the non-amblyopic eye patched (e.g. Li et al., 2011). However, it is unclear whether these patients can benefit merely from patching of the non-amblyopic eye (i.e. no game), the gold standard for amblyopia treatment in children. We addressed this question by directly contrasting the effects of playing action video games with those of patching. Thirty-two amblyopic adults were assigned to either play 40 hours of a dichoptic action game we developed (‘game group’, n=16; see Bayliss et al., 2013), or watch action movies with the non-amblyopic eye patched (‘patching group’, n=16). Following a two months no-contact period, game group participants crossed over to the patching-plus-movies treatment. VA was assessed at baseline and every 13 hours of game/movies treatment. We found that for the game group, VA improved by 26% on average (26%±3.2; p<.000001), regardless of clinical etiology (anisometropia or strabismus). Surprisingly, anisometropic amblyopes (n=7) in the patching group showed VA improvements comparable to those of the game group (n=7; 32%±4.4; p<.0005), and retained the benefits for at least two months after training. In contrast, strabismic amblyopes in the patching group showed no improvement (.01%±6.8). Game group participants maintained their gains throughout the cross-over period. However, no additional benefits from patching were noted during the cross-over period beyond those gained in the game period, for both anisometropic and strabismic amblyopes. We conclude that a dichoptic action game shows promise as viable treatment for amblyopia, as it improves VA for anisometropic and strabismic adult amblyopes, and the improvements are retained for at least two months following training. Supervised patching, however, is only effective for anisometropic amblyopes.

Voltage-sensitive dye imaging of transcranial magnetic stimulation-induced intracortical dynamics

Article

Full-text available

Sep 2014

Significance Transcranial magnetic stimulation (TMS) is significant for medical diagnostics, therapeutic treatment, and basic brain research. However, highly resolved observations of its immediate effects remained obscured because existing techniques are limited in spatial or temporal resolutions and are severely disturbed by the high magnetic fields. Here, we avoid these limitations, using optical imaging with voltage-sensitive dye (VSD) in the cat animal model. VSD transforms changes in neuronal membrane voltage into optical signals, providing microsecond resolution and evading contamination by electromagnetic artifacts. We visualize TMS-induced cortical dynamics and characterize effects on visual processing over scales of milliseconds, minutes, and hours. Combined TMS and VSD imaging offers a powerful approach to study targeted modifications in cortical function during TMS-based plasticity and learning protocols.

Assessing Binocular Interaction in Amblyopia and Its Clinical Feasibility

Article

Full-text available

Jun 2014
PLOS ONE

Purpose To measure binocular interaction in amblyopes using a rapid and patient-friendly computer-based method, and to test the feasibility of the assessment in the clinic. Methods Binocular interaction was assessed in subjects with strabismic amblyopia (n = 7), anisometropic amblyopia (n = 6), strabismus without amblyopia (n = 15) and normal vision (n = 40). Binocular interaction was measured with a dichoptic phase matching task in which subjects matched the position of a binocular probe to the cyclopean perceived phase of a dichoptic pair of gratings whose contrast ratios were systematically varied. The resulting effective contrast ratio of the weak eye was taken as an indicator of interocular imbalance. Testing was performed in an ophthalmology clinic under 8 mins. We examined the relationships between our binocular interaction measure and standard clinical measures indicating abnormal binocularity such as interocular acuity difference and stereoacuity. The test-retest reliability of the testing method was also evaluated. Results Compared to normally-sighted controls, amblyopes exhibited significantly reduced effective contrast (∼20%) of the weak eye, suggesting a higher contrast requirement for the amblyopic eye compared to the fellow eye. We found that the effective contrast ratio of the weak eye covaried with standard clincal measures of binocular vision. Our results showed that there was a high correlation between the 1st and 2nd measurements (r = 0.94, p<0.001) but without any significant bias between the two. Conclusions Our findings demonstrate that abnormal binocular interaction can be reliably captured by measuring the effective contrast ratio of the weak eye and quantitative assessment of binocular interaction is a quick and simple test that can be performed in the clinic. We believe that reliable and timely assessment of deficits in a binocular interaction may improve detection and treatment of amblyopia.

Time Course of Dichoptic Masking in Normals and Suppression in Amblyopes

Article

Full-text available

Apr 2014

Purpose: To better understand the relationship between dichoptic masking in normal vision and suppression in amblyopia we address three questions: First, what is the time course of dichoptic masking in normals and amblyopes? Second, is interocular suppression low-pass or band-pass in its spatial dependence? And third, in the above two regards, is dichoptic masking in normals different from amblyopic suppression? Methods: We measured the dependence of dichoptic masking in normal controls and amblyopes on the temporal duration of presentation under three conditions; monocular (the nontested eye-i.e., dominant eye of normals or nonamblyopic eye of amblyopes, being patched), dichoptic-luminance (the nontested eye seeing a mean luminance-i.e., a DC component) and dichoptic-contrast (the nontested eye seeing high-contrast visual noise). The subject had to detect a letter in the other eye, the contrast of which was varied. Results: We found that threshold elevation relative to the patched condition occurred in both normals and amblyopes when the nontested eye saw either 1/f or band-pass filtered noise, but not just mean luminance (i.e., there was no masking from the DC component that corresponds to a channel responsive to a spatial frequency of 0 cyc/deg); longer presentation of the target (corresponding to lower temporal frequencies) produced greater threshold elevation. Conclusions: Dichoptic masking exhibits similar properties in both subject groups, being low-pass temporally and band-pass spatially, so that masking was greatest at the longest presentation durations and was not greatly affected by mean luminance in the nontested eye.

Binocular Training Reduces Amblyopic Visual Acuity Impairment

Article

Full-text available

Mar 2014
Strabismus

Abstract Amblyopia is the most common cause of monocular visual impairment. Patching, which is modestly effective, is the current treatment of amblyopia in children. There is no clinically approved treatment for adults. The present study is a clinical trial (non-sham controlled and non-randomized) that assessed the efficacy of binocular training for improvement of the visual acuity in children and adults with amblyopia. Twenty-two amblyopic subjects ranging in age from 5 to 73 (mean: 36.2) years for whom patching and/or surgical treatments did not correct their visual impairment completed an average of 14.5 sessions of binocular training over a period of 4 to 6 weeks. Random dot kinematograms were presented dichoptically to the two eyes and the participants' task was to identify the direction of motion of the targets. Mean visual acuity improvement was 0.34 LogMAR (range: 0.1-0.58 LogMAR) and was shown to persist 6 months following the cessation of binocular training. Our study provides results in a large number of patients that confirm the clinical effectiveness of binocular training as a treatment for amblyopia in improving visual acuity in both children and adults. Moreover, this study is the first to demonstrate that the improvements in visual function were maintained for 6 months in the absence of any additional treatment.

Strabismus Disrupts Binocular Synaptic Integration in Primary Visual Cortex

Article

Full-text available

Oct 2013
J NEUROSCI

Visual disruption early in development dramatically changes how primary visual cortex neurons integrate binocular inputs. The disruption is paradigmatic for investigating the synaptic basis of long-term changes in cortical function, because the primary visual cortex is the site of binocular convergence. The underlying alterations in circuitry by visual disruption remain poorly understood. Here we compare membrane potential responses, observed via whole-cell recordings in vivo, of primary visual cortex neurons in normal adult cats with those of cats in which strabismus was induced before the developmental critical period. In strabismic cats, we observed a dramatic shift in the ocular dominance distribution of simple cells, the first stage of visual cortical processing, toward responding to one eye instead of both, but not in complex cells, which receive inputs from simple cells. Both simple and complex cells no longer conveyed the binocular information needed for depth perception based on binocular cues. There was concomitant binocular suppression such that responses were weaker with binocular than with monocular stimulation. Our estimates of the excitatory and inhibitory input to single neurons indicate binocular suppression that was not evident in synaptic excitation, but arose de novo because of synaptic inhibition. Further constraints on circuit models of plasticity result from indications that the ratio of excitation to inhibition evoked by monocular stimulation decreased mainly for nonpreferred eye stimulation. Although we documented changes in synaptic input throughout primary visual cortex, a circuit model with plasticity at only thalamocortical synapses is sufficient to account for our observations.

Non-Invasive Brain Stimulation in Neglect Rehabilitation: An Update

Article

Full-text available

Jun 2013
FRONT HUM NEUROSCI

Here, we review the effects of non-invasive brain stimulation such as transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS) in the rehabilitation of neglect. We found 12 studies including 172 patients (10 TMS studies and 2 tDCS studies) fulfilling our search criteria. Activity of daily living measures such as the Barthel Index or, more specifically for neglect, the Catherine Bergego Scale were the outcome measure in three studies. Five studies were randomized controlled trials with a follow-up time after intervention of up to 6 weeks. One TMS study fulfilled criteria for Class I and one for Class III evidence. The studies are heterogeneous concerning their methodology, outcome measures, and stimulation parameters making firm comparisons and conclusions difficult. Overall, there are however promising results for theta-burst stimulation, suggesting that TMS is a powerful add-on therapy in the rehabilitation of neglect patients.

Interocular suppression in amblyopia for global orientation processing

Article

Full-text available

Apr 2013
J VISION

We developed a dichoptic global orientation coherence paradigm to quantify interocular suppression in amblyopia. This task is biased towards ventral processing and allows comparison with two other techniques-global motion processing, which is more dorsally biased, and binocular phase combination, which most likely reflects striate function. We found a similar pattern for the relationship between coherence threshold and interocular contrast curves (thresholds vs. interocular contrast ratios or TvRs) in our new paradigm compared with those of the previous dichoptic global motion coherence paradigm. The effective contrast ratios at balance point (where the signals from the two eyes have equal weighting) in our new paradigm were larger than those of the dichoptic global motion coherence paradigm but less than those of the binocular phase combination paradigm. The measured effective contrast ratios in the three paradigms were also positively correlated with each other, with the two global coherence paradigms having the highest correlation. We concluded that: (a) The dichoptic global orientation coherence paradigm is effective in quantifying interocular suppression in amblyopia; and (b) Interocular suppression, while sharing a common suppression mechanism at the early stage in the pathway (e.g., striate cortex), may have additional extra-striate contributions that affect both dorsal and ventral streams differentially.

Anodal Transcranial Direct Current Stimulation Reduces Psychophysically Measured Surround Suppression in the Human Visual Cortex

Article

Full-text available

May 2012
PLOS ONE

Transcranial direct current stimulation (tDCS) is a safe, non-invasive technique for transiently modulating the balance of excitation and inhibition within the human brain. It has been reported that anodal tDCS can reduce both GABA mediated inhibition and GABA concentration within the human motor cortex. As GABA mediated inhibition is thought to be a key modulator of plasticity within the adult brain, these findings have broad implications for the future use of tDCS. It is important, therefore, to establish whether tDCS can exert similar effects within non-motor brain areas. The aim of this study was to assess whether anodal tDCS could reduce inhibitory interactions within the human visual cortex. Psychophysical measures of surround suppression were used as an index of inhibition within V1. Overlay suppression, which is thought to originate within the lateral geniculate nucleus (LGN), was also measured as a control. Anodal stimulation of the occipital poles significantly reduced psychophysical surround suppression, but had no effect on overlay suppression. This effect was specific to anodal stimulation as cathodal stimulation had no effect on either measure. These psychophysical results provide the first evidence for tDCS-induced reductions of intracortical inhibition within the human visual cortex.

The Role of Suppression in Amblyopia

Article

Full-text available

Mar 2011

This study had three main goals: to assess the degree of suppression in patients with strabismic, anisometropic, and mixed amblyopia; to establish the relationship between suppression and the degree of amblyopia; and to compare the degree of suppression across the clinical subgroups within the sample. Using both standard measures of suppression (Bagolini lenses and neutral density [ND] filters, Worth 4-Dot test) and a new approach involving the measurement of dichoptic motion thresholds under conditions of variable interocular contrast, the degree of suppression in 43 amblyopic patients with strabismus, anisometropia, or a combination of both was quantified. There was good agreement between the quantitative measures of suppression made with the new dichoptic motion threshold technique and measurements made with standard clinical techniques (Bagolini lenses and ND filters, Worth 4-Dot test). The degree of suppression was found to correlate directly with the degree of amblyopia within our clinical sample, whereby stronger suppression was associated with a greater difference in interocular acuity and poorer stereoacuity. Suppression was not related to the type or angle of strabismus when this was present or the previous treatment history. These results suggest that suppression may have a primary role in the amblyopia syndrome and therefore have implications for the treatment of amblyopia.

Different resting state brain activity and functional connectivity in patients who respond and not to bifrontal tDCS for tinnitus suppression

Article

Full-text available

Mar 2011
EXP BRAIN RES

Tinnitus is an ongoing phantom percept. It has been demonstrated that bifrontal transcranial direct current stimulation (tDCS) can reduce tinnitus. In this study, one group of patients reported a substantial improvement in their tinnitus perception, whereas another group described minor or no beneficial effect at all. The objective was to verify whether the activity and connectivity of the resting brain is different for people who will respond to bifrontal tDCS for tinnitus in comparison with non-responders. Higher gamma band activity was demonstrated in right primary and secondary auditory cortex and right parahippocampus for responders. It has been shown that gamma band activity in the auditory cortex is correlated with tinnitus loudness and that the anterior cingulate is involved in tinnitus distress. People who were going to respond to bifrontal tDCS also demonstrated an increased functional connectivity in the gamma band between the right dorsolateral prefrontal cortex (DLPFC) and the right parahippocampus as well as the right DLPFC and subgenual anterior cingulate cortex (sgACC). An analysis revealed that responders to bifrontal tDCS also experienced a larger suppression effect on TMS placed over the right temporal cortex (i.e. auditory cortex) than non-responders. Responders to bifrontal tDCS seem to differ in resting brain activity compared to non-responders in the right auditory cortex and parahippocampal area. They also have a different functional connectivity between DLPFC and, respectively, the sgACC and parahippocampal area. These connectivities might explain the suppression effect for both tinnitus loudness and tinnitus-related distress.

Physiological Basis of Transcranial Direct Current Stimulation

Article

Full-text available

Feb 2011
NEUROSCIENTIST

Since the rediscovery of transcranial direct current stimulation (tDCS) about 10 years ago, interest in tDCS has grown exponentially. A noninvasive stimulation technique that induces robust excitability changes within the stimulated cortex, tDCS is increasingly being used in proof-of-principle and stage IIa clinical trials in a wide range of neurological and psychiatric disorders. Alongside these clinical studies, detailed work has been performed to elucidate the mechanisms underlying the observed effects. In this review, the authors bring together the results from these pharmacological, neurophysiological, and imaging studies to describe their current knowledge of the physiological effects of tDCS. In addition, the theoretical framework for how tDCS affects motor learning is proposed.

Neuronal Responses in Visual Area V2 (V2) of Macaque Monkeys with Strabismic Amblyopia

Article

Full-text available

Aug 2011
CEREB CORTEX

Amblyopia, a developmental disorder of spatial vision, is thought to result from a cascade of cortical deficits over several processing stages beginning at the primary visual cortex (V1). However, beyond V1, little is known about how cortical development limits the visual performance of amblyopic primates. We quantitatively analyzed the monocular and binocular responses of V1 and V2 neurons in a group of strabismic monkeys exhibiting varying depths of amblyopia. Unlike in V1, the relative effectiveness of the affected eye to drive V2 neurons was drastically reduced in the amblyopic monkeys. The spatial resolution and the orientation bias of V2, but not V1, neurons were subnormal for the affected eyes. Binocular suppression was robust in both cortical areas, and the magnitude of suppression in individual monkeys was correlated with the depth of their amblyopia. These results suggest that the reduced functional connections beyond V1 and the subnormal spatial filter properties of V2 neurons might have substantially limited the sensitivity of the amblyopic eyes and that interocular suppression was likely to have played a key role in the observed alterations of V2 responses and the emergence of amblyopia.

A new binocular approach to the treatment of Amblyopia in adults well beyond the critical period of visual development

Article

Full-text available

Jan 2010

The present treatments for amblyopia are predominantly monocular aiming to improve the vision in the amblyopic eye through either patching of the fellow fixing eye or visual training of the amblyopic eye. This approach is problematic, not least of which because it rarely results in establishment of binocular function. Recently it has shown that amblyopes possess binocular cortical mechanisms for both threshold and suprathreshold stimuli. We outline a novel procedure for measuring the extent to which the fixing eye suppresses the fellow amblyopic eye, rendering what is a structurally binocular system, functionally monocular. Here we show that prolonged periods of viewing (under the artificial conditions of stimuli of different contrast in each eye) during which information from the two eyes is combined leads to a strengthening of binocular vision in strabismic amblyopes and eventual combination of binocular information under natural viewing conditions (stimuli of the same contrast in each eye). Concomitant improvement in monocular acuity of the amblyopic eye occurs with this reduction in suppression and strengthening of binocular fusion. Furthermore, in a majority of patients tested, stereoscopic function is established. This provides the basis for a new treatment of amblyopia, one that is purely binocular and aimed at reducing suppression as a first step.

GABA Concentration Is Reduced in Visual Cortex in Schizophrenia and Correlates with Orientation-Specific Surround Suppression

Article

Full-text available

Mar 2010
J NEUROSCI

The neural mechanisms underlying cognitive deficits in schizophrenia remain essentially unknown. The GABA hypothesis proposes that reduced neuronal GABA concentration and neurotransmission results in cognitive impairments in schizophrenia. However, few in vivo studies have directly examined this hypothesis. We used magnetic resonance spectroscopy (MRS) at high field to measure visual cortical GABA levels in 13 subjects with schizophrenia and 13 demographically matched healthy control subjects. We found that the schizophrenia group had an approximately 10% reduction in GABA concentration. We further tested the GABA hypothesis by examining the relationship between visual cortical GABA levels and orientation-specific surround suppression (OSSS), a behavioral measure of visual inhibition thought to be dependent on GABAergic synaptic transmission. Previous work has shown that subjects with schizophrenia exhibit reduced OSSS of contrast discrimination (Yoon et al., 2009). For subjects with both MRS and OSSS data (n = 16), we found a highly significant positive correlation (r = 0.76) between these variables. GABA concentration was not correlated with overall contrast discrimination performance for stimuli without a surround (r = -0.10). These results suggest that a neocortical GABA deficit in subjects with schizophrenia leads to impaired cortical inhibition and that GABAergic synaptic transmission in visual cortex plays a critical role in OSSS.

Promoting neurological recovery of function via metaplasticity

Article

Full-text available

Dec 2009

The modification of synapses by neural activity has been proposed to be the substrate for experience-dependent brain development, learning, and recovery of visual function after brain injury. The effectiveness or ‘strength‘ of synaptic transmission can be persistently modified in response to defined patterns of pre- and post-synaptic activity. Well-studied examples of this type of synaptic plasticity are long-term potentiation and long-term depression. Can we exploit the current understanding of these mechanisms in order to strengthen brain connections that may have been weakened or impaired by sensory deprivation, disease or injury? Theoretically motivated research in the visual cortex has suggested ways to promote synaptic potentiation. The theoretical concept is that the type and extent of synaptic plasticity caused by patterns of activity depend critically on the recent prior history of synaptic or cellular activity. Studies in visual cortex strongly support this concept, and have suggested a mechanism for ‘metaplasticity‘ – the plasticity of synaptic plasticity – based on activity-dependent modification of NMDA-receptor structure and function. The knowledge gained by these studies suggests ways in which recovery of function can be promoted.

Polarity-Sensitive Modulation of Cortical Neurotransmitters by Transcranial Stimulation

Article

Full-text available

May 2009
J NEUROSCI

Transcranial direct current stimulation (tDCS) modulates cortical excitability and is being used for human studies more frequently. Here we probe the underlying neuronal mechanisms by measuring polarity-specific changes in neurotransmitter concentrations using magnetic resonance spectroscopy (MRS). MRS provides evidence that excitatory (anodal) tDCS causes locally reduced GABA while inhibitory (cathodal) stimulation causes reduced glutamatergic neuronal activity with a highly correlated reduction in GABA, presumably due to the close biochemical relationship between the two neurotransmitters.

Clinical suppression and amblyopia

Article

Full-text available

Apr 1988
INVEST OPHTH VIS SCI

In individuals with abnormal binocular vision, such as strabismics and anisometropes, it is common for all or part of one eye's view to be suppressed so binocular confusion and diplopia are eliminated. We examined the relation between the depth of suppression (the amount by which the monocular contrast increment threshold for an eye was elevated by stimulation in the contralateral eye) and the degree of amblyopia (difference in monocular contrast thresholds for the two eyes). There was a significant negative correlation between suppression and amblyopia, so that clinical suppressors with no amblyopia exhibited deep suppression (ie, large threshold elevation) while observers with amblyopia exhibited weaker or no suppression. This negative correlation was found when the two eyes viewed orthogonally oriented contours as well as identically oriented contours. These results suggest that when an eye is amblyopic there is no longer a need for strong suppression of that eye by the contralateral eye.

The role of suppression in amblyopia

Article

Sep 2011

Purpose This study had three main aims; to assess the degree of suppression in patients with strabismic, anisometropic and mixed amblyopia, to establish the relationship between suppression and the degree of amblyopia and to compare the degree of suppression across the clinical sub‐groups within our sample. Methods Using both standard measures of suppression (Bagolini lenses and ND filters, Worth 4 dots) and a new approach involving the measurement of dichoptic motion thresholds under conditions of variable interocular contrast, we quantified the degree of suppression in 43 amblyopic patients with strabismus, anisometropia or a combination of both. Results There was good agreement between the quantitative measures of suppression made using the new dichoptic motion threshold technique and measurements made using standard clinical techniques (Bagolini lenses and ND filters, Worth 4 dots). The degree of suppression was found to directly correlate with the degree of amblyopia within our clinical sample whereby stronger suppression was associated with a greater interocular acuity difference and poorer stereoacuity. Suppression was not related to the type or angle of strabismus when this was present or the previous treatment history. Conclusion These results suggest that suppression may have a primary role in the amblyopia syndrome and therefore have implications for the treatment of amblyopia.

Risk of amblyopia recurrence after cessation of treatment

Article

Oct 2004
J AAPOS

Background: Although amblyopia can be Successfully treated with patching or atropine, there have been few prospective studies of amblyopia recurrence once treatment is discontinued. Methods: We enrolled 156 children with successfully treated anisometropic or strabismic amblyopia (145 completed follow-up), who were younger than 8 years of age and who received continuous amblyopia treatment for the previous 3 months (prescribed at least 2 hours of daily patching or prescribed at least one drop of atropine per week) and who had improved at least 3 logMAR levels during the period of continuous treatment. Patients were followed off treatment for 52 weeks to assess recurrence of amblyopia, defined as a 2 or more logMAR level reduction of visual acuity from enrollment, confirmed by a second examination. Recurrence was also considered to have occurred if treatment was restarted because of a nonreplicated 2 or more logMAR level reduction of visual acuity. Results. Recurrence occurred in 35 (24%) of 145 cases (95% confidence interval 17% to 32%) and was similar in patients who stopped patching (25%) and in patients who stopped atropine (21%). In patients treated with moderately intense patching (6 to 8 hours per day), recurrence was more common (11 of 26; 42%) when treatment was not reduced prior to cessation than when treatment was reduced to 2 hours per day prior to cessation (3 of 22; 14%, odds ratio 4.4, 95% confidence interval 1.0 to 18.7). Conclusions. Approximately one fourth of successfully treated amblyopic children experience a recurrence within the first year off treatment. For patients treated with 6 or more hours of daily patching, our data suggest that the risk of recurrence is greater when patching is stopped abruptly rather than when it is reduced to 2 hours per day prior to cessation. A randomized clinical trial of no weaning versus weaning in successfully-treated amblyopia is warranted to confirm these observational findings.

The iPod binocular home-based treatment for amblyopia in adults: Efficacy and compliance

Article

Aug 2014
CLIN EXP OPTOM

Background: Occlusion therapy for amblyopia is predicated on the idea that amblyopia is primarily a disorder of monocular vision; however, there is growing evidence that patients with amblyopia have a structurally intact binocular visual system that is rendered functionally monocular due to suppression. Furthermore, we have found that a dichoptic treatment intervention designed to directly target suppression can result in clinically significant improvement in both binocular and monocular visual function in adult patients with amblyopia. The fact that monocular improvement occurs in the absence of any fellow eye occlusion suggests that amblyopia is, in part, due to chronic suppression. Previously the treatment has been administered as a psychophysical task and more recently as a video game that can be played on video goggles or an iPod device equipped with a lenticular screen. The aim of this case-series study of 14 amblyopes (six strabismics, six anisometropes and two mixed) ages 13 to 50 years was to investigate: 1. whether the portable video game treatment is suitable for at-home use and 2. whether an anaglyphic version of the iPod-based video game, which is more convenient for at-home use, has comparable effects to the lenticular version. Methods: The dichoptic video game treatment was conducted at home and visual functions assessed before and after treatment. Results: We found that at-home use for 10 to 30 hours restored simultaneous binocular perception in 13 of 14 cases along with significant improvements in acuity (0.11 ± 0.08 logMAR) and stereopsis (0.6 ± 0.5 log units). Furthermore, the anaglyph and lenticular platforms were equally effective. In addition, the iPod devices were able to record a complete and accurate picture of treatment compliance. Conclusion: The home-based dichoptic iPod approach represents a viable treatment for adults with amblyopia.

Binocular vision in amblyopia: Structure, suppression and plasticity

Article

Mar 2014
OPHTHAL PHYSL OPT

The amblyopic visual system was once considered to be structurally monocular. However, it now evident that the capacity for binocular vision is present in many observers with amblyopia. This has led to new techniques for quantifying suppression that have provided insights into the relationship between suppression and the monocular and binocular visual deficits experienced by amblyopes. Furthermore, new treatments are emerging that directly target suppressive interactions within the visual cortex and, on the basis of initial data, appear to improve both binocular and monocular visual function, even in adults with amblyopia. The aim of this review is to provide an overview of recent studies that have investigated the structure, measurement and treatment of binocular vision in observers with strabismic, anisometropic and mixed amblyopia.

Binocular iPad treatment for amblyopia

Conference Paper

Jan 2013

PurposeMonocular amblyopia treatment (patching or penalization) does not always result in 6/6 vision and amblyopia often recurs. As amblyopia arises from abnormal binocular visual experience, we evaluated the effectiveness of a novel home-based binocular amblyopia treatment.Methods Children (4-12 y) wore anaglyphic glasses to play binocular games on an iPad platform for 4 h/w for 4 weeks. The first 25 children were assigned to sham games and then 50 children to binocular games. Children in the binocular group had the option of participating for an additional 4 weeks. Compliance was monitored with calendars and tracking fellow eye contrast settings. About half of the children in each group were also treated with patching at a different time of day. Best-corrected visual acuity, suppression, and stereoacuity were measured at baseline, at the 4- and 8-week outcome visits, and 3 months after cessation of treatment.ResultsMean (±SE) visual acuity improved in the binocular group from 0.47±0.03 logMAR at baseline to 0.39±0.03 logMAR at 4 weeks (P<0.001); there was no significant change for the sham group. The effect of binocular games on visual acuity did not differ for children who were patched vs those who were not. The median stereoacuity remained unchanged in both groups. An additional 4 weeks of treatment did not yield additional visual acuity improvement. Visual acuity improvements were maintained for 3 months after the cessation of treatment.Conclusions Binocular iPad treatment rapidly improved visual acuity, and visual acuity was stable for at least 3 months following the cessation of treatment.Eye advance online publication, 25 July 2014; doi:10.1038/eye.2014.165.

Transcranial Direct Current Stimulation Enhances Recovery of Stereopsis in Adults With Amblyopia

Article

Jul 2013
NEUROTHERAPEUTICS

Amblyopia is a neurodevelopmental disorder of vision caused by abnormal visual experience during early childhood that is often considered to be untreatable in adulthood. Recently, it has been shown that a novel dichoptic videogame-based treatment for amblyopia can improve visual function in adult patients, at least in part, by reducing inhibition of inputs from the amblyopic eye to the visual cortex. Non-invasive anodal transcranial direct current stimulation has been shown to reduce the activity of inhibitory cortical interneurons when applied to the primary motor or visual cortex. In this double-blind, sham-controlled cross-over study we tested the hypothesis that anodal transcranial direct current stimulation of the visual cortex would enhance the therapeutic effects of dichoptic videogame-based treatment. A homogeneous group of 16 young adults (mean age 22.1 ± 1.1 years) with amblyopia were studied to compare the effect of dichoptic treatment alone and dichoptic treatment combined with visual cortex direct current stimulation on measures of binocular (stereopsis) and monocular (visual acuity) visual function. The combined treatment led to greater improvements in stereoacuity than dichoptic treatment alone, indicating that direct current stimulation of the visual cortex boosts the efficacy of dichoptic videogame-based treatment. This intervention warrants further evaluation as a novel therapeutic approach for adults with amblyopia.

Noninvasive brain stimulation: From physiology to network dynamics and back

Article

Jun 2013
NAT NEUROSCI

Noninvasive brain stimulation techniques have been widely used for studying the physiology of the CNS, identifying the functional role of specific brain structures and, more recently, exploring large-scale network dynamics. Here we review key findings that contribute to our understanding of the mechanisms underlying the physiological and behavioral effects of these techniques. We highlight recent innovations using noninvasive stimulation to investigate global brain network dynamics and organization. New combinations of these techniques, in conjunction with neuroimaging, will further advance the utility of their application.

Anodal Transcranial Direct Current Stimulation Transiently Improves Contrast Sensitivity and Normalizes Visual Cortex Activation in Individuals With Amblyopia

Article

Jun 2013
NEUROREHAB NEURAL RE

Background: Amblyopia is a neurodevelopmental disorder of vision that is associated with abnormal patterns of neural inhibition within the visual cortex. This disorder is often considered to be untreatable in adulthood because of insufficient visual cortex plasticity. There is increasing evidence that interventions that target inhibitory interactions within the visual cortex, including certain types of noninvasive brain stimulation, can improve visual function in adults with amblyopia. Objective: We tested the hypothesis that anodal transcranial direct current stimulation (a-tDCS) would improve visual function in adults with amblyopia by enhancing the neural response to inputs from the amblyopic eye. Methods: Thirteen adults with amblyopia participated and contrast sensitivity in the amblyopic and fellow fixing eye was assessed before, during and after a-tDCS or cathodal tDCS (c-tDCS). Five participants also completed a functional magnetic resonance imaging (fMRI) study designed to investigate the effect of a-tDCS on the blood oxygen level-dependent response within the visual cortex to inputs from the amblyopic versus the fellow fixing eye. Results: A subgroup of 8/13 participants showed a transient improvement in amblyopic eye contrast sensitivity for at least 30 minutes after a-tDCS. fMRI measurements indicated that the characteristic cortical response asymmetry in amblyopes, which favors the fellow eye, was reduced by a-tDCS. Conclusions: These preliminary results suggest that a-tDCS deserves further investigation as a potential tool to enhance amblyopia treatment outcomes in adults.

Long Lasting Effects of Daily Theta Burst rTMS Sessions in the Human Amblyopic Cortex

Article

Apr 2013
BRAIN STIMUL

Background: It has been reported that a single session of 1 Hz or 10 Hz repetitive transcranial magnetic stimulation (rTMS) of the visual cortex can temporarily improve contrast sensitivity in adults with amblyopia. More recently, continuous theta burst stimulation (cTBS) of the visual cortex has been found to improve contrast sensitivity in observers with normal vision. Objective/hypothesis: The aims of this study were to assess whether cTBS of the visual cortex could improve contrast sensitivity in adults with amblyopia and whether repeated sessions of cTBS would lead to more pronounced and/or longer lasting effects. Methods: cTBS was delivered to the visual cortex while patients viewed a high contrast stimulus with their non-amblyopic eye. This manipulation was designed to bias the effects of cTBS toward inputs from the amblyopic eye. Contrast sensitivity was measured before and after stimulation. The effects of one cTBS session were measured in five patients and the effects of five consecutive daily sessions were measured in four patients. Three patients were available for follow-up at varying intervals after the final session. Results: cTBS improved amblyopic eye contrast sensitivity to high spatial frequencies (P < 0.05) and there was a cumulative improvement across sessions with asymptotic improvement occurring after 2 daily sessions of stimulation. The contrast sensitivity improvements were stable over a period of up to 78 days. Conclusions: These initial results in a small number of patients indicate the cTBS may allow for enduring visual function improvements in adults with amblyopia.

Quantitative Measurement of Interocular Suppression in Anisometropic Amblyopia A Case-Control Study

Article

Apr 2013

Objective: The aims of this study were to assess (1) the relationship between interocular suppression and visual function in patients with anisometropic amblyopia, (2) whether suppression can be simulated in matched controls using monocular defocus or neutral density filters, (3) the effects of spectacle or rigid gas-permeable contact lens correction on suppression in patients with anisometropic amblyopia, and (4) the relationship between interocular suppression and outcomes of occlusion therapy. Design: Case-control study (aims 1-3) and cohort study (aim 4). Participants: Forty-five participants with anisometropic amblyopia and 45 matched controls (mean age, 8.8 years for both groups). Methods: Interocular suppression was assessed using Bagolini striated lenses, neutral density filters, and an objective psychophysical technique that measures the amount of contrast imbalance between the 2 eyes that is required to overcome suppression (dichoptic motion coherence thresholds). Visual acuity was assessed using a logarithm minimum angle of resolution tumbling E chart and stereopsis using the Randot preschool test. Main outcome measures: Interocular suppression assessed using dichoptic motion coherence thresholds. Results: Patients exhibited significantly stronger suppression than controls, and stronger suppression was correlated significantly with poorer visual acuity in amblyopic eyes. Reducing monocular acuity in controls to match that of cases using neutral density filters (luminance reduction) resulted in levels of interocular suppression comparable with that in patients. This was not the case for monocular defocus (optical blur). Rigid gas-permeable contact lens correction resulted in less suppression than spectacle correction, and stronger suppression was associated with poorer outcomes after occlusion therapy. Conclusions: Interocular suppression plays a key role in the visual deficits associated with anisometropic amblyopia and can be simulated in controls by inducing a luminance difference between the eyes. Accurate quantification of suppression using the dichoptic motion coherence threshold technique may provide useful information for the management and treatment of anisometropic amblyopia. Financial disclosure(s): Proprietary or commercial disclosure may be found after the references.

A push-pull treatment for strengthening the ‘lazy eye’ in amblyopia

Article

Apr 2013

Almost all individuals exhibit sensory eye dominance, one neural basis of which is unequal interocular inhibition. Sensory eye dominance can impair binocular functions that depend on both excitatory and inhibitory mechanisms [1 • Sengpiel F. • Blakemore C. • Kind P.C. • Harrad R. Interocular suppression in the visual cortex of strabismic cats.J. Neurosci. 1994; 14: 6855-6871 • PubMed • Google Scholar , 2 • Su Y. • He Z.J. • Ooi T.L. Coexistence of binocular integration and suppression determined by surface border information.Proc. Natl. Acad. Sci. USA. 2009; 106: 15990-15995 • Crossref • PubMed • Scopus (24) • Google Scholar , 3 • Xu J.P. • He Z.J. • Ooi T.L. A binocular perimetry study of the causes and implications of sensory eye dominance.Vis. Res. 2011; 51: 2386-2397 • Crossref • PubMed • Scopus (22) • Google Scholar ]. We developed a ‘push-pull’ perceptual learning protocol that simultaneously affects the excitatory and inhibitory networks to reduce sensory eye dominance and improve stereopsis in adults with otherwise normal vision [4 • Xu J.P. • He Z.J. • Ooi T.L. Effectively reducing sensory eye dominance with a push–pull perceptual learning protocol.Curr. Biol. 2010; 20: 1864-1868 • Abstract • Full Text • Full Text PDF • PubMed • Scopus (35) • Google Scholar ]. The push-pull protocol provides a promising clinical paradigm for treating the extreme sensory eye dominance in amblyopia (‘lazy eye’). The prevailing standard of care does not directly treat sensory eye dominance; instead, selected excitatory functions in the amblyopic eye are stimulated while the strong eye is patched, on the assumption that recovery of the weak eye’s excitatory functions rebalances the eyes. Patching the strong eye does not directly address interocular inhibition; in contrast, the push-pull protocol by design excites the weak eye, while completely inhibiting the strong eye’s perception to recalibrate the interocular balance of excitatory and inhibitory interactions. Here, we show that three adult amblyopes who trained on the push-pull protocol gained longstanding improvements in interocular balance and stereopsis. Our findings provide a proof-of-concept and evidence that push-pull learning leads to long-term plasticity.

Dichoptic training enables the adult amblyopic brain to learn

Article

Apr 2013

Adults with amblyopia, a common visual cortex disorder caused primarily by binocular disruption during an early critical period, do not respond to conventional therapy involving occlusion of one eye [1]. But it is now clear that the adult human visual cortex has a significant degree of plasticity [2], suggesting that something must be actively preventing the adult brain from learning to see through the amblyopic eye. One possibility is an inhibitory signal from the contralateral eye that suppresses cortical inputs from the amblyopic eye [3,4]. Such a gating mechanism could explain the apparent lack of plasticity within the adult amblyopic visual cortex [5,6]. Here we provide direct evidence that alleviating suppression of the amblyopic eye through dichoptic stimulus presentation induces greater levels of plasticity than forced use of the amblyopic eye alone. This indicates that suppression is a key gating mechanism that prevents the amblyopic brain from learning to see.

Amblyopia and Binocular Vision

Article

Nov 2012

Eileen E Birch

Amblyopia is the most common cause of monocular visual loss in children, affecting 1.3% to 3.6% of children. Current treatments are effective in reducing the visual acuity deficit but many amblyopic individuals are left with residual visual acuity deficits, ocular motor abnormalities, deficient fine motor skills, and risk for recurrent amblyopia. Using a combination of psychophysical, electrophysiological, imaging, risk factor analysis, and fine motor skill assessment, the primary role of binocular dysfunction in the genesis of amblyopia and the constellation of visual and motor deficits that accompany the visual acuity deficit has been identified. These findings motivated us to evaluate a new, binocular approach to amblyopia treatment with the goals of reducing or eliminating residual and recurrent amblyopia and of improving the deficient ocular motor function and fine motor skills that accompany amblyopia.

Interocular suppression in normal and amblyopic vision: Spatio-temporal properties

Article

Oct 2012
J VISION

We measured the properties of interocular suppression in strabismic amblyopes and compared these to dichoptic masking in binocularly normal observers. We used a dichoptic version of the well-established probed-sinewave paradigm that measured sensitivity to a brief target stimulus (one of four letters to be discriminated) in the amblyopic eye at different times relative to a suppression-inducing mask in the fixing eye. This was done using both sinusoidal steady state and transient approaches. The suppression-inducing masks were either modulations of luminance or contrast (full field, just overlaying the target, or just surrounding the target). Our results were interpreted using a descriptive model that included contrast gain control and spatio-temporal filtering prior to excitatory binocular combination. The suppression we measured, other than in magnitude, was not fundamentally different from normal dichoptic masking: lowpass spatio-temporal properties with similar contributions from both surround and overlay suppression.

The BCM theory of synapse modification at 30: Interaction of theory with experiment

Article

Nov 2012

Thirty years have passed since the publication of Elie Bienenstock, Leon Cooper and Paul Munro's 'Theory for the development of neuron selectivity: orientation specificity and binocular interaction in visual cortex', known as the BCM theory of synaptic plasticity. This theory has guided experimentalists to discover some fundamental properties of synaptic plasticity and has provided a mathematical structure that bridges molecular mechanisms and systems-level consequences of learning and memory storage.

Quantitative measurement of interocular suppression in children with amblyopia

Article

Jun 2012

In this study we explored the possibility of using a dichoptic global motion technique to measure interocular suppression in children with amblyopia. We compared children (5-16 years old) with unilateral anisometropic and/or strabismic amblyopia to age-matched control children. Under dichoptic viewing conditions, contrast interference thresholds were determined with a global motion direction-discrimination task. Using virtual reality goggles, high contrast signal dots were presented to the amblyopic eye, while low contrast noise dots were presented to the non-amblyopic fellow eye. The contrast of the noise dots was increased until discrimination of the motion direction of the signal dots reached chance performance. Contrast interference thresholds were significantly lower in the strabismic group than in the anisometropic and control group. Our results suggest that interocular suppression is stronger in strabismic than in anisometropic amblyopia.

From motor cortex to visual cortex: The application of noninvasive brain stimulation to amblyopia

Article

Apr 2012
DEV PSYCHOBIOL

Noninvasive brain stimulation is a technique for inducing changes in the excitability of discrete neural populations in the human brain. A current model of the underlying pathological processes contributing to the loss of motor function after stroke has motivated a number of research groups to investigate the potential therapeutic application of brain stimulation to stroke rehabilitation. The loss of motor function is modeled as resulting from a combination of reduced excitability in the lesioned motor cortex and an increased inhibitory drive from the nonlesioned hemisphere over the lesioned hemisphere. This combination of impaired neural function and pathological suppression resonates with current views on the cause of the visual impairment in amblyopia. Here, we discuss how the rationale for using noninvasive brain stimulation in stroke rehabilitation can be applied to amblyopia, review a proof-of-principle study demonstrating that brain stimulation can temporarily improve amblyopic eye function, and propose future research avenues.

An Exploratory Study: Prolonged Periods of Binocular Stimulation Can Provide an Effective Treatment for Childhood Amblyopia

Article

Dec 2011

The purpose of the present study was to explore the potential for treating childhood amblyopia with a binocular stimulus designed to correlate the visual input from both eyes. Eight strabismic, two anisometropic, and four strabismic and anisometropic amblyopes (mean age, 8.5 ± 2.6 years) undertook a dichoptic perceptual learning task for five sessions (each lasting 1 hour) over the course of a week. The training paradigm involved a simple computer game, which required the subject to use both eyes to perform the task. A statistically significant improvement (t(₁₃) = 5.46; P = 0.0001) in the mean visual acuity (VA) of the amblyopic eye (AE) was demonstrated, from 0.51 ± 0.27 logMAR before training to 0.42 ± 0.28 logMAR after training with six subjects gaining 0.1 logMAR or more of improvement. Measurable stereofunction was established for the first time in three subjects with an overall significant mean improvement in stereoacuity after training (t(₁₃) =2.64; P = 0.02). The dichoptic-based perceptual learning therapy employed in the present study improved both the monocular VA of the AE and stereofunction, verifying the feasibility of a binocular approach in the treatment of childhood amblyopia.

Do tDCS and TMS influence tinnitus transiently via a direct cortical and indirect somatosensory modulating effect? A combined TMS-tDCS and TENS study

Article

Oct 2011
BRAIN STIMUL

Tinnitus is usually defined as an intrinsic sound percept that cannot be attributed to an external sound source that tinnitus can be suppressed by neuromodulation techniques such as transcranial direct current stimulation (tDCS), transcranial magnetic stimulation (TMS), and transcranial electrical nerve stimulation (TENS). It is thought that TMS and tDCS modulate tinnitus directly by targeting the frontal and/or auditory cortex of the brain, whereas TENS most likely influences tinnitus indirectly via cervical nerve-cochlear nucleus interactions. It is unknown whether part of the tinnitus modulating effect of tDCS and TMS also depends on a somatosensory modulating effect analogous to TENS, via the trigeminal and cervical nerves. We aimed to investigate this question by analyzing to which extent response to one neuromodulation technique predicts the response to another neuromodulation technique. We analyzed 153 patients with chronic tinnitus (> 1 year) who underwent all three neuromodulation techniques (C2 nerve TENS, auditory cortex TMS, and bifrontal tDCS). Our results show that TENS predicts tDCS and TMS better than the opposite, and tDCS predicts TMS response and vice versa. On the basis of these results, it is it is argued that TENS only modulates the tinnitus brain circuit indirectly, whereas TMS and tDCS have a dual working mechanism, a TENS-like mechanism plus a direct brain modulating mechanism.

Modulation of cortical inhibition by rTMS – Findings obtained from animal models

Article

Jul 2011
J PHYSIOL-LONDON

Transcranial magnetic stimulation (TMS) has become a popular method to non-invasively stimulate the human brain. The opportunity to modify cortical excitability with repetitive stimulation (rTMS) has especially gained interest for its therapeutic potential. However, details of the cellular mechanisms of the effects of rTMS are scarce. Currently favoured are long-term changes in the efficiency of excitatory synaptic transmission, with low-frequency rTMS depressing it, but high-frequency rTMS augmenting. Only recently has modulation of cortical inhibition been considered as an alternative way to explain lasting changes in cortical excitability induced by rTMS. Adequate animal models help to highlight stimulation-induced changes in cellular processes which are not assessable in human rTMS studies. In this review article, we summarize findings obtained with our rat models which indicate that distinct inhibitory cell classes, like the fast-spiking cells characterized by parvalbumin expression, are most sensitive to certain stimulation protocols, e.g. intermittent theta burst stimulation. We discuss how our findings can support the recently suggested models of gating and homeostatic plasticity as possible mechanisms of rTMS-induced changes in cortical excitability.

Brain Plasticity in the Adult: Modulation of Function in Amblyopia with rTMS

Article

Jul 2008
CURR BIOL

Amblyopia is a cortically based visual disorder caused by disruption of vision during a critical early developmental period. It is often thought to be a largely intractable problem in adult patients because of a lack of neuronal plasticity after this critical period [1]; however, recent advances have suggested that plasticity is still present in the adult amblyopic visual cortex [2-6]. Here, we present data showing that repetitive transcranial magnetic stimulation (rTMS) of the visual cortex can temporarily improve contrast sensitivity in the amblyopic visual cortex. The results indicate continued plasticity of the amblyopic visual system in adulthood and open the way for a potential new therapeutic approach to the treatment of amblyopia.

A Game Platform for Treatment of Amblyopia

Article

Feb 2011
IEEE T NEUR SYS REH

We have developed a prototype device for take-home use that can be used in the treatment of amblyopia. The therapeutic scenario we envision involves patients first visiting a clinic, where their vision parameters are assessed and suitable parameters are determined for therapy. Patients then proceed with the actual therapeutic treatment on their own, using our device, which consists of an Apple iPod Touch running a specially modified game application. Our rationale for choosing to develop the prototype around a game stems from multiple requirements that such an application satisfies. First, system operation must be sufficiently straightforward that ease-of-use is not an obstacle. Second, the application itself should be compelling and motivate use more so than a traditional therapeutic task if it is to be used regularly outside of the clinic. This is particularly relevant for children, as compliance is a major issue for current treatments of childhood amblyopia. However, despite the traditional opinion that treatment of amblyopia is only effective in children, our initial results add to the growing body of evidence that improvements in visual function can be achieved in adults with amblyopia.

Effect of Amblyopia on Self-Esteem in Children

Article

Dec 2008
OPTOMETRY VISION SCI

In an investigation of the psychosocial impact of amblyopia on children, the perceived self-esteem of children who had been treated for amblyopia was compared with that of age-matched controls. The influence of amblyopia condition or treatment factors that may impact self-perception scores was also explored. Children with a history of treatment for amblyopia (n = 47; age 9.2 +/- 1.3 years) and age-matched controls (n = 52; age 9.4 +/- 0.5 years) completed a standardized age-appropriate questionnaire based evaluation of perceived self-esteem (Harter Self Perception Profile for Children). Their vision characteristics and treatment regimen were also recorded. Bivariate correlation analysis was used to investigate the amblyopic characteristics and treatment factors that may have influenced self-perception scores in the amblyopic group. Children treated for amblyopia had significantly lower social acceptance scores than age-matched control children. In other areas related to self-esteem, including scholastic competence, physical appearance, athletic competence, behavioral conduct and global self worth, amblyopic children gave scores similar to those of control children. Within the amblyopic group, a lower social acceptance score was significantly correlated with a history of treatment with patching but not with a history of strabismus or wearing of glasses. Self-perception of social acceptance was lower in children treated for amblyopia compared with age-matched controls. A reduction in these scores was associated with a history of patching treatment but not with a history of strabismus or spectacle wear.

State-dependency in brain stimulation studies of perception and cognition

Article

Nov 2008
TRENDS COGN SCI

We address the importance of understanding initial states of neuronal populations and of state-dependent responses in cognitive neuroscience experiments with special emphasis on brain stimulation studies of perception and cognition. The approach we present is based on evidence that behavioural and perceptual effects of transcranial magnetic stimulation (TMS) are determined by initial neural activation state; by systematically manipulating neural activation states before application of TMS, one can selectively target specific, even spatially overlapping neural populations within the affected region. This approach is potentially of great benefit to cognitive neuroscience and remediation programmes as it combines high spatial and functional resolution with the ability to assess causality.

Measurement of suprathreshold binocular interactions in amblyopia

Article

Sep 2008

It has been established that in amblyopia, information from the amblyopic eye (AME) is not combined with that from the fellow fixing eye (FFE) under conditions of binocular viewing. However, recent evidence suggests that mechanisms that combine information between the eyes are intact in amblyopia. The lack of binocular function is most likely due to the imbalanced inputs from the two eyes under binocular conditions [Baker, D. H., Meese, T. S., Mansouri, B., & Hess, R. F. (2007b). Binocular summation of contrast remains intact in strabismic amblyopia. Investigative Ophthalmology & Visual Science, 48(11), 5332-5338]. We have measured the extent to which the information presented to each eye needs to differ for binocular combination to occur and in doing so we quantify the influence of interocular suppression. We quantify these suppressive effects for suprathreshold processing of global stimuli for both motion and spatial tasks. The results confirm the general importance of these suppressive effects in rendering the structurally binocular visual system of a strabismic amblyope, functionally monocular.

The threshold contrast sensitivity function in strabismic amblyopia: Evidence for a two type classification

Article

Feb 1977
VISION RES

Threshold contrast sensitivity functions for 10 representative strabismic amblyopes are presented. The results indicate that there are two classes of response. For one class, contrast sensitivity is depressed for only high spatial frequencies. For the other class, contrast sensitivity is depressed for all spatial frequencies, including low spatial frequencies; this response has not been previously reported. It is proposed that some results from the latter class are not simply extensions in severity of the former class and therefore two types of amblyopia need to be postulated.

Prelimary results of a physiologically based treatment of amblyopia

Article

Dec 1978

An apparatus has been developed in which high-contrast square-wave gratings are rotated in front of the amblyopic eye while the child is performing some task requiring visual concentration. In the course of three 7-minute treatments 73% of patients treated achieved 6/12 or better; 75% of these patients had previously undertaken conventional or minimal occlusion.

Spatio temporal interactions in anisometropic and strabismic amblyopia

Article

Feb 1977
INVEST OPHTH VIS SCI

Contrast sensitivity functions for sinusoidal gratings of different spatial frequencies and stimulus durations have been determined for both eyes of amblyopic subjects. For both long and short stimulus durations, the entire contrast sensitivity function of the amblyopic eyes is lower than that of the nonamblyopic eyes. When the gratings were flickered at 10 Hz, the sensitivity for pattern and flicker detection were similar for both eyes at low spatial frequencies. Possible neural mechanisms for the differences in contrast sensitivity are considered with respect to recent psychophysical and electrophysiological evidence for channels with different spatio-temporal properties in the mammalian visual system.

Binocular integration of contrast information in amblyopia

Article

Dec 1992
VISION RES

We asked whether suppression in amblyopia could be accounted for by dichoptic masking as described in normals, operating in the presence of a contrast threshold difference between the two eyes. A dichoptic masking paradigm was employed to investigate binocular interaction in a mixed group of amblyopic subjects. Normal dichoptic masking was not seen after threshold differences between the two eyes were accounted for in the majority of subjects studied. We found that the binocular dysfunction did not merely follow as a consequence of the known monocular loss and that it depended upon the aetiology of the amblyopia and the spatial frequency of the stimulus.

Noninvasive Magnetic Stimulation of the Human Motor Cortex

Article

Jun 1985

Amblyopia and the binocular approach to its Therapy

Abstract

No full-text available

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