OBJECTIVE: 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.

Amblyopia is a neurodevelopmental disorder of the visual system that impairs the vision of millions of children worldwide. Amblyopia is best treated within the sensitive period of visual development when a child is up to seven years of age. Currently, the gold standard for early treatment of childhood amblyopia is patching, with new treatments emerging in recent years. We aim to evaluate the effectiveness of these newly developed treatments for amblyopia in children aged seven years and younger while comparing them to the current industry standard of patching. We searched online databases including PubMed, Google Scholar, and Cochrane Library for randomized controlled trials (RCTs), systematic reviews, meta-analyses, and narrative reviews relating to amblyopia treatment in children aged seven and younger. We only included articles and studies completed within the last five years and those written in the English language. After compiling a list of 297 articles, we removed duplicates, articles without an available full text, and those not relevant to our topic. Of the remaining 51 articles, we were left with 22 after reading abstracts and removing further irrelevant articles. We did a quality assessment on the remaining 22 articles and were left with 14 articles for our systematic review after removing eight low-quality articles. Of the 14 articles, we had eight RCTs, two systematic reviews, one comparative interventional study, and three narrative reviews. Seven of the articles contained data reinforcing the effectiveness of patching while comparing it to other treatment modalities. Three of the articles had data supporting spectacle correction, including a novel form called alternative flicker glass which delivers occlusion therapy via a spectacle frame with unique lenses, and ultimately deemed it at least as effective or more than patching. Data from three articles supported the use of surgery to successfully correct the angle of strabismus. Findings from five articles backed the use of pharmacologic therapy, specifically atropine when used alongside patching as a more effective alternative to patching solely. However, levodopa plus patching had no advantage over patching alone. Additionally, seven articles addressed the use of virtual reality (VR) and dichoptic therapy as prospective treatments for childhood amblyopia. VR therapy proved beneficial when used within one week after strabismus surgery. Dichoptic training was also effective in improving amblyopic-eye visual acuity when used on its own or in conjunction with spectacles. Furthermore, dichoptic movie therapy was found to be more effective than patching. Thus, we found multiple highly effective treatments for childhood amblyopia that are as effective or more than patching. Future studies should consider prescribing these treatments to larger cohorts while also performing a cost-benefit analysis for each treatment. In addition, more needs to be learned about the potential adverse side effects of these treatments, especially for pharmaceutical therapy.

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.

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.

BACKGROUND: Interest in developing alternative methods for the treatment of amblyopia has long been a topic of interest among clinicians and researchers, as prescribed occlusion and penalization therapies do not always provide an effective response and are associated with a high risk of recurrence and non-compliance. Here, we present the protocol of a small-scale RCT to evaluate the safety and clinical efficacy of a novel VR-based system designed to provide binocular vision training to children with anisometropic amblyopia.
METHODS: We aim to recruit a total of 60 children with anisometropic amblyopia aged 5-17 years with no previous treatment for amblyopia other than refractive correction from the pediatric ophthalmology units of the University Clinical Hospital of Valladolid and the Vithas Medimar International Hospital of Alicante. Children who meet the eligibility criteria and consent to participate will be randomly assigned to a three-month intervention group of 18 half-hour in-office therapy sessions with the NEIVATECH system (group A) or to a parallel group receiving 2 hours of conventional patching per day at home for the same period of time (group B). Assessments of visual function will be carried out before the intervention and at 1, 2 and 3 months, with changes in distance BCVA being the primary outcome measure to be considered. Patient safety, compliance, satisfaction and acceptance to treatment will also be assessed after therapy as other valuable outcome measures. In addition, a rsfMRI scan will be performed on a subgroup of 5 patients from each group at the pre-intervention visit and at the post-intervention visit to test the effects of both therapies on neural plasticity in the visual cortex.
CONCLUSIONS: The NEIVATECH system has been conceived as a serious game designed to provide binocular vision training to anisometropic amblyopic children by complementing the concepts of perceptual learning, dichoptic training and gamification in an immersive VR environment. We hope that this novel approach may lead to greater improvements in vision performance than those provided so far by conventional patching in anisometropic amblyopic children.
BACKGROUND: This protocol was registered with ClinicalTrials.gov ( NCT04819386 ) on 29 March 2021.

Recent clinical trials failed to endorse dichoptic training for amblyopia treatment. Here, we proposed an alternative training strategy that focused on reducing signal threshold contrast in the amblyopic eye under a constant and high noise contrast in the fellow eye (HNC), and compared it to a typical dichoptic strategy that aimed at increasing the tolerable noise contrast in the fellow eye (i.e., TNC strategy). We recruited 16 patients with amblyopia and divided them into two groups. Eight patients in Group 1 received the HNC training, while the other eight patients in Group 2 performed the TNC training first (Phase 1) and then crossed over to the HNC training (Phase 2). We measured contrast sensitivity functions (CSFs) separately in the amblyopic and fellow eyes when the untested eye viewed mean luminance (monocularly unmasked) or noise stimuli (dichoptically masked) before and after training at a particular frequency. The area under the log contrast sensitivity function (AULCSF) of masked and unmasked conditions, and dichoptic gain (the ratio of AULCSF of masked to unmasked condition) were calculated for each eye. We found that both dichoptic training paradigms substantially improved masked CSF, dichoptic gain, and visual acuity in the amblyopic eye. As opposed to the TNC paradigm, the HNC training produced stronger effects on masked CSFs, stereoacuity, dichoptic gain, and visual acuity in the amblyopic eye. Interestingly, the second-phase HNC training in Group 2 also induced further improvement in the masked contrast sensitivity and AULCSF in the amblyopic eye. We concluded that the HNC training strategy was more effective than the TNC training paradigm. Future design for dichoptic training should not only focus on increasing the tolerable noise contrast in the fellow eye but should also \"nurture\" the amblyopic eye under normal binocular viewing conditions and sustained interocular suppression.

Active vision therapy using perceptual learning and/or dichoptic or binocular environments has shown its potential effectiveness in amblyopia, but some doubts remain about the type of stimuli and the mode and sequence of presentation that should be used. A search was performed in PubMed, obtaining 143 articles with information related to the stimuli used in amblyopia rehabilitation, as well as to the neural mechanisms implied in such therapeutic process. Visual deficits in amblyopia and their neural mechanisms associated are revised, including visual acuity loss, contrast sensitivity reduction and stereopsis impairment. Likewise, the most appropriate stimuli according to the literature that should be used for an efficient rehabilitation of the amblyopic eye are described in detail, including optotypes, Gabor\'s patches, random-dot stimuli and Vernier\'s stimuli. Finally, the properties of these stimuli that can be modified during the visual training are discussed, as well as the psychophysical method of their presentation and the type of environment used (perceptual learning, dichoptic stimulation or virtual reality). Vision therapy using all these revised concepts can be an effective option for treating amblyopia or accelerating the treatment period when combining with patching. It is essential to adapt the stimuli to the patient\'s individual features in both monocular and binocular training.

Anisometropic amblyopia is unilateral by definition and current treatment recommendations reflect that characteristic. However, recent research suggests a binocular component that deserves consideration. The aim of this review is to consider the levels of anisometropia deemed amblyogenic, and the cortical changes that occur in the presence of anisometropic amblyopia. Particular attention is given to cortical changes that impact the binocularity of these individuals. Knowledge of binocular deficits in anisometropic amblyopia has implications for current, accepted treatment regimens which are monocular in nature. Therefore, the integrity of binocular function in anisometropic amblyopia and its impact on the visual outcome will be evaluated. Given the rise in binocular treatments under clinical trial for amblyopia, this review also aims to evaluate the evidence of potentially enhanced benefits to anisometropic amblyopes from proposed new binocular therapies.

OBJECTIVE: The purpose of this review is to provide an update on current management and recent research for amblyopia treatment. Part I will review patching, atropine penalization, and pharmacological treatments. Part II will focus on perceptual learning, video gaming, and binocular dichoptic approaches.
METHODS: A literature search was performed in PubMed, ClinicalTrials.gov , Google Scholar, and reference lists of retrieved articles until December 20, 2018, for all papers containing \"amblyopia treatment\" or \"amblyopia therapy.\" We have included RCTs, prospective observational studies, prospective and retrospective cohort studies, pilot studies, and review articles.
RESULTS: The mainstay of treatment for amblyopia has been based on increasing visual stimulation of the amblyopic eye by occlusion, atropine, or optical penalization of the dominant eye. It has been established that refractive adaptation alone can significantly enhance visual acuity. However, the duration of optical correction varies between studies and the effectiveness of spectacle wear over early beginning of patching is still under investigation. Additionally, by means of occlusion dose monitors, it was found that adherence to occlusion affects the outcome, as a dose-response relationship exists between adherence and visual acuity. Treatment efficiency declines with age; however, recent evidence indicates cortical plasticity beyond the \"critical period\" and recommends that an attempt at treatment should be offered to all amblyopic children regardless of age, including those in later childhood. Novel approaches targeted to the restoration of binocular functions, such as perceptual learning, video gaming, and dichoptic training, have shown small effects on visual acuity and have failed to demonstrate non-inferiority over standard treatments.
CONCLUSIONS: On review, significant evidence for the successful management of amblyopia, with occlusion therapy and atropine, has been found. However, the management of amblyopia remains challenging, mainly due to compliance issues and suboptimal treatment outcomes during occlusion and atropine penalization. Recent studies have found evidence of new ways of treating amblyopia particularly in regard to binocular treatment although these remain under investigation. Further robust clinical trials on these new treatment modalities are still warranted in order to establish their role in treating amblyopia.

Dichoptic training is a recent focus of research on perceptual learning in adults with amblyopia, but whether and how dichoptic training is superior to traditional monocular training is unclear. Here we investigated whether dichoptic training could further boost visual acuity and stereoacuity in monocularly well-trained adult amblyopic participants. During dichoptic training the participants used the amblyopic eye to practice a contrast discrimination task, while a band-filtered noise masker was simultaneously presented in the non-amblyopic fellow eye. Dichoptic learning was indexed by the increase of maximal tolerable noise contrast for successful contrast discrimination in the amblyopic eye. The results showed that practice tripled maximal tolerable noise contrast in 13 monocularly well-trained amblyopic participants. Moreover, the training further improved stereoacuity by 27% beyond the 55% gain from previous monocular training, but unchanged visual acuity of the amblyopic eyes. Therefore our dichoptic training method may produce extra gains of stereoacuity, but not visual acuity, in adults with amblyopia after monocular training.