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Neural Plasticity
Volume 2019, Article ID 6208414, 12 pages
https://doi.org/10.1155/2019/6208414
Research Article

Contribution of Short-Time Occlusion of the Amblyopic Eye to a Passive Dichoptic Video Treatment for Amblyopia beyond the Critical Period

1Department of Ophthalmology, CHU NORD, Marseille, France
2Institut de Neurosciences de la Timone (INT), Centre National de la Recherche Scientifique (CNRS) and Aix-Marseille Université (AMU), Marseille, France
3Centre Paradis Monticelli, Marseille, France
4McGill Vision Research, Department of Ophthalmology and Visual Sciences, McGill University, Montreal, Quebec, Canada

Correspondence should be addressed to Alexandre Reynaud; ac.lligcm.liam@duanyer.erdnaxela

Received 22 January 2019; Revised 29 April 2019; Accepted 17 June 2019; Published 28 August 2019

Guest Editor: Claudia Lunghi

Copyright © 2019 Lauren Sauvan et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Dichoptic movie viewing has been shown to significantly improve visual acuity in amblyopia in children. Moreover, short-term occlusion of the amblyopic eye can transiently increase its contribution to binocular fusion in adults. In this study, we first asked whether dichoptic movie viewing could improve the visual function of amblyopic subjects beyond the critical period. Secondly, we tested if this effect could be enhanced by short-term monocular occlusion of the amblyopic eye. 17 subjects presenting stable functional amblyopia participated in this study. 10 subjects followed 6 sessions of 1.5 hour of dichoptic movie viewing (nonpatched group), and 7 subjects, prior to each of these sessions, had to wear an occluding patch over the amblyopic eye for two hours (patched group). Best-corrected visual acuity, monocular contrast sensitivity, interocular balance, and stereoacuity were measured before and after the training. For the nonpatched group, mean amblyopic eye visual acuity significantly improved from 0.54 to 0.46 logMAR (). For the patched group, mean amblyopic eye visual acuity significantly improved from 0.62 to 0.43 logMAR (). Stereoacuity improved significantly when the data of both groups were combined. No significant improvement was observed for the other visual functions tested. Our training procedure combines modern video technologies and recent fundamental findings in human plasticity: (i) long-term plasticity induced by dichoptic movie viewing and (ii) short-term adaptation induced by temporary monocular occlusion. This passive dichoptic movie training approach is shown to significantly improve visual acuity of subjects beyond the critical period. The addition of a short-term monocular occlusion to the dichoptic training shows promising trends but was not significant for the sample size used here. The passive movie approach combined with interocular contrast balancing even over such a short period as 2 weeks has potential as a clinical therapy to treat amblyopia in older children and adults.

1. Introduction

Amblyopia is a neurodevelopmental disorder arising from abnormal visual experience during childhood over a period called “the period of susceptibility” or “the critical period” [15]. It mainly manifests itself by a loss of binocular function, reduced visual acuity in one eye, the amblyopic eye, and it is the most frequent cause of unilateral visual loss in childhood. Its prevalence is around 1-3% of the general population [612]. The presently accepted treatment for amblyopia consists of full optical correction [13] and monocular patching of the nonamblyopic eye to force the use of the amblyopic eye [14]. This treatment is only successful for young children, and it has been assumed that older children and particularly adults lack sufficient brain plasticity. Thus, no treatment is offered to these older patients as their amblyopia is thought to be fixed [15, 15, 16].

It is now well established that amblyopia is associated with cortical dysfunction at monocular and binocular sites [1721]. One binocular theory suggested that it is the consequence of an excess of interocular suppression [2224]. Therefore, binocular training strategies have emerged, focusing on treating the primary binocular disorder [2537]. These are based on dichoptic image presentation that the subject needs to binocularly combine to have full information content of a global motion stimulus [24], a video game [27, 28, 38], a movie [36, 39, 40], or an altered reality device [25, 41]. Binocular fusion only occurs if the contrast of the image seen by the nonamblyopic eye is reduced sufficiently to address the interocular imbalance resulting from suppression. At first, such strategies involved an active participation of the subjects playing a dichoptic video game where success depended on using information simultaneously presented to each eye [27, 28, 31, 35, 38, 4246]. There is also evidence that video game training in general can aid bilateral amblyopia [47].

However, not all patients want to play video games, and some children/adults are so amblyopic that it is not possible to resolve the features necessary to play video games. Hence, more recently, a general application of the same contrast balancing principles has been applied to natural scene stimuli with either passive dichoptic movie watching [36, 37] or augmented reality [25]. These procedures are based on the presentation of complementary images in the two eyes. Passive dichoptic movie watching resulted in benefits for visual acuity in children [36, 39] but has not been tested on adults yet. In principle, this method could be applied to the passive viewing of any video content such as sporting programs, movies, or children’s animations [40]. Here, we tested this procedure for the first time on amblyopic adults and children with stable and resistant amblyopia which could not be treated with standard procedures.

Binocular training methods are an improvement on the current patching approach because they are better accepted [31, 37] and they aim to obtain a better binocular outcome. They engage binocular viewing and in doing so improve the visual acuity of the amblyopic eye. They are thought to operate by utilizing the residual brain plasticity that remains after the critical period of visual development. Recently, another approach has also demonstrated the residual visual plasticity in normal adults [38, 39]. This involves changes in ocular dominance that occur after just 1-2 hours of monocular occlusion. Interestingly, this short-term monocular occlusion results in a strengthening of the deprived eye which is the opposite of what occurs during the critical period in early life. This shift in dominance is only transient, lasting about 1 hour [4851]. This has also been shown in adults with amblyopia [52]. The dominance shift for amblyopes is in the same direction as that found for normals, namely, the deprived eye becomes stronger, but it can be of larger magnitude and longer duration. Thus, the binocular imbalance that characterizes amblyopia can be manipulated for a certain duration by occluding the amblyopic eye, the opposite of classical patching therapy. The hypothesis is that the decrease in sensory stimulation during the deprivation induces a contrast gain increment to boost the sensitivity of the patched eye. Since it occurs rapidly, the mechanism underlying this contrast gain increment is suspected to involve a change of the excitatory/inhibitory balance [4854]. However, this relatively rapid patching effect (few hours) may be quite different to more standard binocular training procedures which operate on a relatively long timescale (weeks). These long-term training procedures may involve a different plasticity mechanism, for example, by establishing new synaptic connections [55, 56].

In this study, we ask whether binocular training based on passive dichoptic movie viewing could, by way of a change in brain plasticity, increase the visual function of subjects with a stable amblyopia who are beyond the normal treatment period for classical patching. Secondly, we wondered if the effects of such a dichoptic treatment protocol could be enhanced by short-term monocular occlusion, specifically carrying out the training during the time window where the occlusion has temporarily rebalanced the excitation-inhibition ratio. To answer this question, we combined these two approaches and asked the subjects to wear an eye patch for two hours prior to undergoing binocular training sessions involving passive dichoptic movie watching.

2. Material and Methods

2.1. Participants

17 amblyopic subjects were included in our study aged from 9 to 67 yo, mean age 34 yo. The criteria for including subjects in the experiment were the following. Subjects had to present with functional amblyopia, secondary to strabismus or anisometropia or both. Their visual acuity had to be stable for at least one year before inclusion, and children under 12 years old had to go through at least six months of conventional occlusion therapy to make sure that amblyopia was stable and resistant. Best-corrected visual acuity (BCVA) in the amblyopic eye had to be higher or equal to 0.2 logMAR, or BCVA difference between the two eyes had to be at least equal to 0.2 logMAR. The strabismus angle had to be lower or equal to 15 prism diopters. We excluded subjects with organic amblyopia, congenital strabismus, presenting any visual or neurologic disease or presenting developmental delay. For the first examination, each participant had to fill out a questionnaire about his/her medical history, and more specifically on the previous treatments, he/she might have had for amblyopia and the observance of these treatments optical correction, occlusion therapy, and strabismus surgery. Clinical details of the amblyopic subjects are reported in Table 1.

Table 1: Characteristics of amblyopic subjects.

Subjects had to wear their full optical correction for all the testing and training procedures. Five subjects who had anisometropia (S1, S7, S8, S9, and S17) did not wear any optical correction before inclusion. For these subjects, we made them wear their adapted optical correction only during testings and dichoptic movie viewing sessions, which was equivalent in total to approximately 12 hours with an optical correction (see Table 1). This is insufficient itself to explain any improvement in the visual functions in terms of spectacle adaptation [13].

Subjects were allocated into one of two intervention groups: the nonpatched group (10 subjects, see details in Table 1), who only followed the dichoptic movie training (see procedures), and the patched group (7 subjects, details in Table 1), who were subjected to monocular occlusion of the amblyopic eye prior to each training session with the dichoptic movies. Subject allocation to each group was mainly determined by their ability to be patched two hours before coming to the lab.

The study took place in the Ophthalmology Department of La Timone Hospital in Marseille. Written informed consent was obtained from all patients or parents/guardians.

2.2. Procedures

Subjects underwent a binocular training procedure. The nonpatched group followed a procedure of six 1.5 hour sessions of dichoptic movie viewing to train their binocular vision similar as in Li et al. [36] (one subject could only undergo 5 sessions, see exact duration per subject in Table 1). The patched group followed the same procedure except that they had to wear an occluding patch over their amblyopic eye for two hours prior to each training session which was removed right before the dichoptic movie viewing. The patch was a standard occlusive adhesive-on-skin Ortopad patch. The patients were shown how to wear the patch in the assessment session. Then, they had to put them on by themselves two hours before they came to the lab for the dichoptic movie viewing session.

A battery of visual function tests detailed below was used to examine the effects of binocular training. It involved monocular visual acuity, contrast sensitivity, interocular balance, and stereosensitivity, tested in that order, each test lasting 5 to 10 minutes. The baseline measures were assessed during a first preliminary assessment session, a few days before the actual beginning of the training. The training outcome measures were realized at the end of the last training session. A follow-up test was also performed approximately one month after the training, but only 10 subjects could come back for this test (see details in Table 1).

2.3. Dichoptic Movie Design

Patients strengthened their binocular vision by passively watching dichoptic movies. A digital mask composed of irregularly shaped blobs was applied on the images seen by the amblyopic eye, and the inverse mask was applied to the images seen by the fellow eye (Figure 1(a) and example Supplementary Movie 1). Therefore, parts of the image were only seen by one eye and complementary parts were only seen by the other eye [36]. Therefore, to perceive a completed coherent picture, it was necessary to combine information seen by both eyes. The shapes and locations of the masks were varied over time. The contrast of the image seen by the amblyopic eye was fixed to its maximum, and the contrast of the image seen by the fellow eye was based on the results of the binocular balance contrast sensitivity baseline measure (Figure 1(b) and example Supplementary Movie 2). Under these conditions of unequal interocular contrasts, suppression is reduced to the point where information can be combined between the two eyes and the videos perceived stably as a coherent whole. These movies were displayed on a linearized wide passive 3D LG 32LB650V 32 screen, , 60 Hz (LG Electronics USA; Englewood, NJ) with polarized glasses at a distance of 120 cm, spanning 32° of visual angle.

Figure 1: Illustration of the dichoptic movies. The two eyes’ views are shown side by side. Complementary patterned image masks composed of irregularly shaped blobs were overlaid over the images seen by the two eyes. The shape and location of the blobs were varied dynamically every 10 seconds. (a) 100% contrast images were presented to the two eyes. (b) A 100% contrast image is presented to the left eye, and an image with a contrast reduced to 40% is presented to the right eye. Movie examples are available as supplementary material. Source video: Lauren Sauvan, wikimedia commons/CC-0.

If the subject perceived the full picture of the movie during a session, then, the contrast in the fellow eye was increased by 10% for the next session. In practice, all subjects always perceived the full picture, and so the contrast was increased in each session. Thus, it happened that it reached the maximal value of 100% for some subjects before the end of the training. Participants confirmed that they could still see the two eye images during each session. This follows the dichoptic balancing principles that have been validated by video games in a number of different studies [2633, 3537].

2.4. Visual Function Assessment
2.4.1. Visual Acuity

Visual acuity was measured using a logarithmic letter chart in standardized conditions (logarithmic visual acuity chart “2000”).

2.4.2. Contrast Sensitivity Function

Monocular contrast sensitivity as a function of spatial frequency was measured using the quick contrast sensitivity function [57]. This is a Bayesian adaptive method which determines the optimal pair of spatial frequency and contrast to test at each trial in order to maximize the information about the contrast sensitivity function. Over the course of 100 trials, the participant had to identify in a single-interval identification task the orientation (horizontal or vertical) of a spatially filtered noise pattern at these set spatial frequencies and contrasts (Figure 2(a)). This method has already been validated on amblyopic subjects [58, 59]. This test was performed on the same equipment as the movie viewing except that participants wore an eyepatch to test monocular vision. Full details of the procedure are given in Reynaud et al. [60].

Figure 2: Test stimuli illustrations. (a) qCSF stimulus illustration. In a single-interval identification task, the subject had to judge the orientation (horizontal or vertical) of a filtered noise pattern of varying spatial frequency and contrast. (b) Dichoptic letter chart illustration. Five letters of 2 c/d were presented at various contrasts to the left eye and 5 different letters with complementary contrasts to the right eye at the same spatial locations. So when viewed with both eyes, letters appeared overlapping on screen. Adapted from Kwon et al. [61]; Birch et al. [62].
2.4.3. Interocular Balance

Interocular balance was measured with the dichoptic letter chart developed by Kwon et al. [61]. This procedure has already been validated on amblyopic subjects [61, 62]. Five letters spatially filtered to a peak spatial frequency of 2 c/d were presented at various contrasts to the left eye and 5 different letters with complementary contrasts to the right eye at the same spatial locations. Therefore, when viewed binocularly, the letters appeared superimposed. The subject had to report the five most visible letters for 10 trials (Figure 2(b)). The relative contrast of the letters seen by each eye was adjusted by an adaptive method [61, 62] in order to determine the interocular balance point for contrast sensitivity. The interocular balance point is expressed as the ratio in dB between the amblyopic and nonamblyopic eye, so a negative value means that the nonamblyopic eye is stronger, a value close to 0 means that the eyes are well-balanced, and a positive value would indicate that the amblyopic eye is stronger. This test was performed on the same equipment as the movie viewing.

2.4.4. Stereosensitivity

Disparity thresholds were measured using the TNO test (Netherlands Organisation for Applied Scientific Research, distributed by Lameris Ootech BV). It is a duochrome test without monocular clue, based on the principles of Julesz’s tests [63], allowing the measurement of stereoscopic acuity from 480 to 15 seconds of arc.

3. Results

We trained 17 subjects, distributed in patched and nonpatched groups (see Materials and Methods) following our protocol to assess the improvement of visual acuity (VA). For most subjects, the VA of the amblyopic eye (AE) improved (lower value in logMAR) at the completion of training compared to before training (the baseline) (see Figure 3(a)). For the nonpatched group (open black symbols), the average value at baseline was logMAR and logMAR at the completion of training. This is a significant improvement of 0.08 logMAR (one-sided Wilcoxon signed rank test, ), which is equivalent to almost one line on the visual acuity chart. For the patched group (filled grey symbols), the average visual acuity of the amblyopic eye was logMAR at baseline and logMAR at the end of training, resulting in an average improvement of 0.19 logMAR, equivalent to almost two lines on the chart. This improvement is also significant (one-sided Wilcoxon signed rank test, ) and remained significant at the one-month follow-up (one-sided Wilcoxon signed rank test, ) whereas it did not quite reach significance for the nonpatched group. To better appreciate these improvements, the difference in VA from baseline is reported in Figure 3(b). The improvement in visual acuity of the amblyopic eye of the participants in the patched group is slightly greater, although this difference is not significant (two-sided Wilcoxon rank sum test, ) and is more long lasting (because it is still significant at the one month follow-up, whereas it is not for the nonpatched group). In both groups, the training did not affect the VA of the nonamblyopic eye with an average improvement of 0.04 and 0.05 logMAR in the patched and nonpatched groups, respectively (two-sided Wilcoxon signed rank test, and , respectively), thus verifying that the improvement was not induced by any learning of the visual acuity measurement itself.

Figure 3: Visual acuity improvement. (a) Visual acuity of the amblyopic eye (AE) of the participants reported at baseline, at the outcome of the training, and at the follow-up control one month later. (b) Visual acuity difference from the baseline of the amblyopic eye. (c) Visual acuity difference from baseline as a function of the initial acuity of the amblyopic eye. Participants from the patched group are indicated with filled grey symbols, and participants of the nonpatched group with open black symbols. Dashed lines represent linear regressions.

In order to test whether the amplitude of the effect we observe depends on the severity of amblyopia, we plot in Figure 3(c) the difference in VA from baseline as a function of the initial acuity of the amblyopic eye. There is no link between the degree of improvement and the initial severity of amblyopia in the nonpatched group (coefficient of determination , ). However, there is a significant correlation between the degree of improvement and the acuity of the AE at baseline in the patched group (, ). The effect is such that in this group, the stronger the amblyopia, the greater the improvement. We did not observe a significant correlation between the amplitude of the effect and the age of the participants in either group (, in the nonpatched group and , in the patched group).

Another monocular function we tested was contrast sensitivity. We measured the average contrast sensitivity of the amblyopic eye as a function of spatial frequency before and after training (Figure 4). For the nonpatched group (Figure 4)(a), the contrast sensitivity function at baseline peaks at approximately 1.5 c/d with an amplitude of 45 (solid line) which is in line with previous reports [58, 59]. At the completion of training, the amplitude reaches 78. For the patched group (Figure 4(b)), the contrast sensitivity function at baseline peaks at approximately 1.5 c/d with an amplitude of 84 (solid line). After training, the amplitude reached 134 with a peak shifted to higher frequencies at 3 c/d. In order to test the significance of these improvements, we reported the gain parameter of the sensitivity function as estimated by the qCSF method [57] for each participant at baseline, at the completion of training, and at the follow-up control, after training had been completed in Figure 4(c). This training improvement is not significant for either the nonpatched or the patched group (one-sided Wilcoxon signed rank test, and , respectively). It is not different between the two groups either (two-sided Wilcoxon rank sum test, ). And there is no significant correlation between the amplitude of the improvement and the gain at baseline in either group (respective , and , in the patched and nonpatched group).

Figure 4: Contrast sensitivity improvement. (a) Contrast sensitivity of the amblyopic eye as a function of spatial frequency at baseline (solid line) and at the training outcome (dashed line) for the nonpatched group. Grey areas represent ±standard error. (b) Contrast sensitivity of the amblyopic eye as a function of spatial frequency at baseline and at the training outcome for the patched group. Same line style as (a). (c) Individual sensitivity gain of the participants at baseline, at the outcome of the training, and at the follow-up control one month later. Participants from the patched group are indicated with filled grey symbols, and participants of the nonpatched group with open black symbols.

Finally, we tested the effect of the training on two binocular functions: the interocular balance and the stereosensitivity (Figure 5). The interocular balance expressed as the ratio in dB between the amblyopic and nonamblyopic eye is reported for each participant in Figure 5(a). The averages of the balance over the nonpatched group at baseline and at the completion of training are, respectively, and . The fact that the value gets closer to zero indicates a small improvement in the balance, although it is not significant (one-sided Wilcoxon signed rank test, ). For the patched group, a better improvement from to was observed; however, this is not significant either (one-sided Wilcoxon signed rank test, ). Even merging, the two groups, this improvement remained not significant (one-sided Wilcoxon signed rank test, ).

Figure 5: Effect of training on binocular vision. (a) Interocular balance amblyopic/nonamblyopic eye expressed in dB at baseline, at the outcome, and at the follow-up of the training. (b) Disparity sensitivity threshold at baseline, at the outcome, and at the follow-up of the training. Participants from the patched group are indicated with filled grey symbols, and participants of the nonpatched group with open black symbols.

For stereosensitivity, among the subjects who initially had stereovision, in the nonpatched group, their average stereo threshold improved from arcmin at baseline to arcmin at the completion of training (Figure 5(b)). However, this improvement was not significant because only four subjects could initially perform the test (one-sided Wilcoxon signed rank test, ). Additionally, one subject (S16) who previously was not able to perform the TNO test showed a measurable stereosensitivity after training (480 arcmin). In the patched group, only two subjects had a measurable stereosensitivity at baseline. Their average stereo threshold improved from arcmin to arcmin, but again, this improvement was not significant due to the small sample size (one-sided Wilcoxon signed rank test, ). Here again, one subject (S14) who was not able to perform the TNO test initially showed a measurable stereosensitivity after training (120 arcmin).

Since there was no statistically significant difference in any measure between the patched and nonpatched groups and since they both were subjected to the same passive dichoptic movie treatment, in order to get more statistical power, we combined the results from the two groups to address the question of whether the treatment per se leads to improvements in visual function in older children and adults with amblyopia. Statistically significant improvements were found in both visual acuity (average improvement from 0.58 to 0.45 logMAR: one-sided Wilcoxon signed rank test, ) and stereopsis ( arcmin to arcmin: one-sided Wilcoxon signed rank test, ). This is the first report of the successful application of this passive approach in amblyopic older children and adults which complements a previous report of its success in younger amblyopic children [36].

4. Discussion

The primary objective of our study was to evaluate the effect of binocular training with passive dichoptic movie viewing on subjects with a stable resistant amblyopia. The training intervention was very minimal compared with classical patching therapy: 9 hours compared with many months. Our results showed that even very short dichoptic movie viewing significantly improved visual acuity of about one line after approximately 9 hours of training over a two-week period; the maximum visual acuity improvement measured was of 3 lines. This improvement is consistent with the results of Bao et al. [25] on teenagers and adults using an altered reality system and Li et al. [36] and Mezad-Koursh et al. [39] on children using passive movie viewing. The visual acuity improvements we observe are comparable with those of Bao et al. (0.08 logMAR improvement in both studies). Although not unexpectedly, they are lower compared to those obtained in children (0.20 logMAR for Li et al. and 0.26 logMAR for Mezad-Koursh et al.). This difference may be explained by the fact that subjects in these studies were children whereas in our study, they were mostly adults, hence showing less plasticity [64].

We also observed an improvement in the monocular peak contrast sensitivity function amplitude, but it was not significant due to the small sample size [25]. Despite the subjects’ ability to appreciate the full picture of the movie while we increased the contrast seen by the fellow eye by 10% for each session, the interocular contrast sensitivity balance remained quite stable after training. Bossi et al. [40] and Li et al. [36] observed similar results, contrary to Hess et al. [26], Li et al. [28], and Kelly et al. [37] who observed a reweighting of this balance proportional to the visual gain. The reason for this is unclear; each of the above studies used a different test for binocular balance. The method used in the study by Kelly et al. [37] is similar to that used in the present study; however, they studied children and we studied adults. It may be possible to improve acuity in the absence of any change in binocular function [36, 40].

Most subjects who had measurable stereoscopic vision with the TNO test at inclusion showed an improvement of it although this was not significant due to the small sample of subjects and the fact that disparities larger than 480 arc seconds could not be measured with the TNO test. Indeed, among the 10 subjects of the nonpatched group, only 4 of them had measurable stereoscopic vision at baseline and all of them improved after training. In this nonpatched group, one patient without measurable stereoscopic vision with the TNO test at baseline exhibited measurable stereopsis after training. Only 2 subjects had measurable stereoscopic vision at baseline in the patched group. One improved and one remained constant after training. In this group, one patient without measurable stereoscopic vision at baseline exhibited measurable stereopsis at final evaluation too. The trend is for stereopsis to improve although owing to limitations in our stereo test [6568] and the reduced stereopsis of our patients. When the results of the two groups were combined, this improvement became statistically significant ( arcmin to arcmin: one-sided Wilcoxon signed rank test, ). This is the first evidence that passive dichoptic movie training improves stereovision in older children and adults with amblyopia.

Our study shows for the first time that a very short period (9 hours) of passive dichoptic movie viewing can improve visual function in adult subjects presenting with a stable and resistant amblyopia. Previously, a similar improvement was shown for an altered reality system in teenagers and adults [25]. One interest of dichoptic movie viewing is its potential to increase compliance in comparison to patching or to other forms of dichoptic training [25, 31, 35, 41, 45, 69, 70]. First of all, because dichoptic movie viewing is passive, it does not require any active participation of the subject, unlike perceptual learning or dichoptic video game play. This is a crucial advantage especially for older subjects who do not want to play video games or even for younger children who may not have the necessary cognitive capabilities. Furthermore, dichoptic movie viewing is very flexible in that it can be used at home and can be adapted to any video content such as virtual or augmented reality approaches [25, 41, 7174].

The secondary objective of our study was to evaluate if the mechanisms involved in short-term monocular occlusion and dichoptic movie training could be complementary and synergistic and, if combined together, result in a larger therapeutic effect. Short-term monocular deprivation might activate binocular brain plasticity mechanisms via changes in the excitatory/inhibitory balance [4850, 52, 75, 76] and that could enhance dichoptic training-based improvements.

We observed a trend that such prior monocular occlusion could enhance the effect of training on visual acuity: our results showed a larger improvement of visual acuity in the patched group (0.19 logMAR, almost 2 lines, maximum gain in this subgroup: 4 lines), in comparison to the nonpatched group (0.08 logMAR, almost 1 line, maximum gain in this subgroup: 2 lines); however, the difference was not significant for our sample size.

Two recent studies examined the effect of intermittent monocular patching of the amblyopic eye 2 h per day as a treatment for amblyopia with procedures comparable to our patching [77, 78]. The Lunghi et al. study also involved physical exercise, and the Zhou et al. study involved more patching sessions. They, respectively, reported improvements of 0.15 and 0.13 logMAR in the acuity of the amblyopic eye which is less than the 0.19 logMAR improvement we observed with the combined patching and dichoptic movie viewing procedure.

We do not observe any correlation between the acuity of the amblyopic eye at baseline and the improvement in the nonpatched group (Figure 3(c)). This could indicate that the dichoptic movie training effect in itself does not depend on the strength of amblyopia and that the difference we observe in the improvement between the two groups is not due to their initial acuity differences. Lunghi et al. [77] do not report such correlation either in their patching combined with exercise study. However, we observe a correlation in the patched group such that the stronger the amblyopia, the greater the improvement. This would indicate that the preliminary patching mostly affects severe cases of amblyopia. One explanation could be that the improvement reaches a saturation level in mild cases whereas the combined patching and dichoptic training method would be the only one powerful enough to show a greater improvement in severe cases.

This trend should be investigated with a much larger sample size and possibly a crossover design because there is a good reason to think that these two approaches (ocular dominance plasticity and dichoptic training) may, because of their different dynamics, be mutually beneficial. Preliminary monocular patching might act on short-term adaptation by altering the inhibitory/excitatory balance allowing a rapid change in contrast gain [4850, 5254]. On the other hand, dichoptic movie training follows a slower course, probably by involving binocular mechanisms similar to perceptual learning [25, 79] resulting in the longer term establishment of new synaptic connections [55, 56, 8082]. Thus, there is every reason to think that the change in the excitatory/inhibitory balance may accelerate and/or amplify the plasticity effect induced by the dichoptic training by inducing a more plastic state in the brain before each training session.

There were trends that did not reach significance between either groups for other visual functions: monocular contrast sensitivity, interocular contrast balance, and stereoscopic vision. The results in each group should be considered independently because the two groups were not homogeneous. Indeed, randomization was not possible because of logistic issues (i.e., preliminary patching was not possible for subjects who were coming to the hospital by car or who were coming very early in the morning). In both groups, the subjects can be considered as their own controls because training did not affect the VA of the nonamblyopic eye; this rules out any hypothesis based on the fact that the improvement could have been a consequence of task learning. Furthermore, all participants were used to watching screens (TV or computer) at least one hour a day (average 3.8 hours a day, see Table 1). Hence, adding 1.5 hour of TV watching every 2-3 days did not drastically change their exposure to digital screens, and so it is very unlikely that the improvement we observe could be solely due to the increased time of screen exposure per se.

Apart from these inconveniences, preliminary monocular patching did not really decrease compliance (qualitative report) to the training because it was the amblyopic eye that was patched [77, 78]; hence, it was much less disabling than patching the fellow eye, and the patching was for a much shorter duration compared to what the subjects were used to.

Our training method shows promising results and could be used to power larger scale randomized controlled trials to validate this type of treatment. These results were obtained in only six sessions over a 2-week period of training. There are a number of recommendations: extend the training to a longer period than 2 weeks, develop a better measure of stereopsis in the coarse disparity range, one that can provide an individual variability measure for better statistical evaluation, produce a more sensitive test of binocular balance, and extend the periods of monocular occlusion to see if its benefits for dichoptic training can be enhanced.

Data Availability

The data used to support the findings of this study are available from the corresponding author upon request.

Conflicts of Interest

McGill University holds two patents related to this dichoptic movie treatment. Drs. Reynaud and Hess are the named inventors. Other authors have no commercial relationships to disclose.

Acknowledgments

This work was supported by a grant from the Agence Régionale de la Santé to LS, a grant from the Fondation de France–Berthe Fouassier to NS, grants from the Canadian Institutes of Health Research (228103) and ERA-NET NEURON (JTC 2015) to RFH, and a FRQS Vision Health Research Network of Quebec networking grant to RFH, FC, and AR.

Supplementary Materials

Supplementary 1. Supplementary Movie 1: example movie with 100% contrast images presented to the two eyes. Source video: Lauren Sauvan, wikimedia commons/CC-0.

Supplementary 2. Supplementary Movie 2: example movie with 100% contrast image presented to the left eye and 40% contrast image presented to the right eye. Source video: Lauren Sauvan, wikimedia commons/CC-0.

References

  1. D. H. Hubel and T. N. Wiesel, “Receptive fields of single neurones in the cat’s striate cortex,” The Journal of Physiology, vol. 148, no. 3, pp. 574–591, 1959. View at Publisher · View at Google Scholar · View at Scopus
  2. D. H. Hubel and T. N. Wiesel, “Shape and arrangement of columns in cat’s striate cortex,” The Journal of Physiology, vol. 165, no. 3, pp. 559–568, 1963. View at Publisher · View at Google Scholar · View at Scopus
  3. D. H. Hubel and T. N. Wiesel, “Effects of monocular deprivation in kittens,” Naunyn-Schmiedebergs Archiv für experimentelle Pathologie und Pharmakologie, vol. 248, no. 6, pp. 492–497, 1964. View at Publisher · View at Google Scholar · View at Scopus
  4. D. H. Hubel and T. N. Wiesel, “Binocular interaction in striate cortex of kittens reared with artificial squint,” Journal of Neurophysiology, vol. 28, no. 6, pp. 1041–1059, 1965. View at Publisher · View at Google Scholar · View at Scopus
  5. D. H. Hubel and T. N. Wiesel, “The period of susceptibility to the physiological effects of unilateral eye closure in kittens,” The Journal of Physiology, vol. 206, no. 2, pp. 419–436, 1970. View at Publisher · View at Google Scholar · View at Scopus
  6. K. Attebo, P. Mitchell, R. Cumming, W. Smith, N. Jolly, and R. Sparkes, “Prevalence and causes of amblyopia in an adult population,” Ophthalmology, vol. 105, no. 1, pp. 154–159, 1998. View at Publisher · View at Google Scholar · View at Scopus
  7. D. S. Friedman, M. X. Repka, J. Katz et al., “Prevalence of amblyopia and strabismus in white and African American children aged 6 through 71 months: the Baltimore Pediatric Eye Disease Study,” Ophthalmology, vol. 116, no. 11, pp. 2128–2134.e2, 2009. View at Publisher · View at Google Scholar · View at Scopus
  8. S. Ganekal, V. Jhanji, Y. Liang, and S. Dorairaj, “Prevalence and etiology of amblyopia in southern India: results from screening of school children aged 5-15 years,” Ophthalmic Epidemiology, vol. 20, no. 4, pp. 228–231, 2013. View at Publisher · View at Google Scholar · View at Scopus
  9. J. H. Groenewoud, A. M. Tjiam, V. K. Lantau et al., “Rotterdam AMblyopia screening effectiveness study: detection and causes of amblyopia in a large birth cohort,” Investigative Ophthalmology & Visual Science, vol. 51, no. 7, pp. 3476–3484, 2010. View at Publisher · View at Google Scholar · View at Scopus
  10. D. Magdalene, H. Bhattacharjee, M. Choudhury et al., “Community outreach: an indicator for assessment of prevalence of amblyopia,” Indian Journal of Ophthalmology, vol. 66, no. 7, pp. 940–944, 2018. View at Publisher · View at Google Scholar · View at Scopus
  11. A. S.-I. Pai, K. A. Rose, J. F. Leone et al., “Amblyopia prevalence and risk factors in Australian preschool children,” Ophthalmology, vol. 119, no. 1, pp. 138–144, 2012. View at Publisher · View at Google Scholar · View at Scopus
  12. C. Wu and D. G. Hunter, “Amblyopia: diagnostic and therapeutic options,” American Journal of Ophthalmology, vol. 141, no. 1, pp. 175–184.e2, 2006. View at Publisher · View at Google Scholar · View at Scopus
  13. S. A. Cotter, A. R. Edwards, D. K. Wallace et al., “Treatment of anisometropic amblyopia in children with refractive correction,” Ophthalmology, vol. 113, no. 6, pp. 895–903, 2006. View at Publisher · View at Google Scholar · View at Scopus
  14. S. E. Dorey, G. G. Adams, J. P. Lee, and J. J. Sloper, “Intensive occlusion therapy for amblyopia,” The British Journal of Ophthalmology, vol. 85, no. 3, pp. 310–313, 2001. View at Publisher · View at Google Scholar · View at Scopus
  15. W. E. Scott and C. F. Dickey, “Stability of visual acuity in amblyopic patients after visual maturity,” Graefe's Archive for Clinical and Experimental Ophthalmology, vol. 226, no. 2, pp. 154–157, 1988. View at Publisher · View at Google Scholar · View at Scopus
  16. C. E. Stewart, M. J. Moseley, D. A. Stephens, and A. R. Fielder, “Treatment dose-response in amblyopia therapy: the Monitored Occlusion Treatment of Amblyopia Study (MOTAS),” Investigative Opthalmology & Visual Science, vol. 45, no. 9, pp. 3048–3054, 2004. View at Publisher · View at Google Scholar · View at Scopus
  17. H. M. Eggers and C. Blakemore, “Physiological basis of anisometropic amblyopia,” Science, vol. 201, no. 4352, pp. 264–267, 1978. View at Publisher · View at Google Scholar · View at Scopus
  18. L. Kiorpes and J. A. Movshon, “Neural limitations on visual development,” in The Visual Neurosciences, L. M. Calupa and J. S. Werner, Eds., pp. 159–173, MIT Press, Cambridge, MA, USA, 2004. View at Google Scholar
  19. L. Kiorpes, D. C. Kiper, L. P. O'Keefe, J. R. Cavanaugh, and J. A. Movshon, “Neuronal correlates of amblyopia in the visual cortex of macaque monkeys with experimental strabismus and anisometropia,” The Journal of Neuroscience, vol. 18, no. 16, pp. 6411–6424, 1998. View at Publisher · View at Google Scholar
  20. S. LeVay, M. Connolly, J. Houde, and D. C. V. Essen, “The complete pattern of ocular dominance stripes in the striate cortex and visual field of the macaque monkey,” The Journal of Neuroscience, vol. 5, no. 2, pp. 486–501, 1985. View at Publisher · View at Google Scholar
  21. C. Shooner, L. E. Hallum, R. D. Kumbhani et al., “Asymmetric dichoptic masking in visual cortex of amblyopic macaque monkeys,” The Journal of Neuroscience, vol. 37, no. 36, pp. 8734–8741, 2017. View at Publisher · View at Google Scholar · View at Scopus
  22. R. F. Hess and B. Thompson, “Amblyopia and the binocular approach to its therapy,” Vision Research, vol. 114, pp. 4–16, 2015. View at Publisher · View at Google Scholar · View at Scopus
  23. D. H. Baker, T. S. Meese, B. Mansouri, and R. F. Hess, “Binocular summation of contrast remains intact in strabismic amblyopia,” Investigative Ophthalmology & Visual Science, vol. 48, no. 11, pp. 5332–5338, 2007. View at Publisher · View at Google Scholar · View at Scopus
  24. B. Mansouri, B. Thompson, and R. F. Hess, “Measurement of suprathreshold binocular interactions in amblyopia,” Vision Research, vol. 48, no. 28, pp. 2775–2784, 2008. View at Publisher · View at Google Scholar · View at Scopus
  25. M. Bao, B. Dong, L. Liu, S. A. Engel, and Y. Jiang, “The best of both worlds: adaptation during natural tasks produces long-lasting plasticity in perceptual ocular dominance,” Psychological Science, vol. 29, no. 1, pp. 14–33, 2018. View at Publisher · View at Google Scholar · View at Scopus
  26. R. F. Hess, B. Mansouri, and B. Thompson, “A new binocular approach to the treatment of amblyopia in adults well beyond the critical period of visual development,” Restorative Neurology and Neuroscience, vol. 28, no. 6, pp. 793–802, 2010. View at Publisher · View at Google Scholar · View at Scopus
  27. L. To, B. Thompson, J. R. Blum, G. Maehara, R. F. Hess, and J. R. Cooperstock, “A game platform for treatment of amblyopia,” IEEE Transactions on Neural Systems and Rehabilitation Engineering, vol. 19, no. 3, pp. 280–289, 2011. View at Publisher · View at Google Scholar · View at Scopus
  28. J. Li, B. Thompson, D. Deng, L. Y. L. Chan, M. Yu, and R. F. Hess, “Dichoptic training enables the adult amblyopic brain to learn,” Current Biology, vol. 23, no. 8, pp. R308–R309, 2013. View at Publisher · View at Google Scholar · View at Scopus
  29. D. P. Spiegel, J. Li, R. F. Hess et al., “Transcranial direct current stimulation enhances recovery of stereopsis in adults with amblyopia,” Neurotherapeutics, vol. 10, no. 4, pp. 831–839, 2013. View at Publisher · View at Google Scholar · View at Scopus
  30. B. Mansouri, P. Singh, A. Globa, and P. Pearson, “Binocular training reduces amblyopic visual acuity impairment,” Strabismus, vol. 22, no. 1, pp. 1–6, 2014. View at Publisher · View at Google Scholar · View at Scopus
  31. R. F. Hess, R. J. Babu, S. Clavagnier, J. Black, W. Bobier, and B. Thompson, “The iPod binocular home-based treatment for amblyopia in adults: efficacy and compliance,” Clinical and Experimental Optometry, vol. 97, no. 5, pp. 389–398, 2014. View at Publisher · View at Google Scholar · View at Scopus
  32. P. J. Knox, A. J. Simmers, L. S. Gray, and M. Cleary, “An exploratory study: prolonged periods of binocular stimulation can provide an effective treatment for childhood amblyopia,” Investigative Ophthalmology & Visual Science, vol. 53, no. 2, pp. 817–824, 2012. View at Publisher · View at Google Scholar · View at Scopus
  33. S. L. Li, R. M. Jost, S. E. Morale et al., “A binocular iPad treatment for amblyopic children,” Eye, vol. 28, no. 10, pp. 1246–1253, 2014. View at Publisher · View at Google Scholar · View at Scopus
  34. E. E. Birch, S. L. Li, R. M. Jost et al., “Binocular iPad treatment for amblyopia in preschool children,” Journal of American Association for Pediatric Ophthalmology and Strabismus, vol. 19, no. 1, pp. 6–11, 2015. View at Publisher · View at Google Scholar · View at Scopus
  35. K. R. Kelly, R. M. Jost, L. Dao, C. L. Beauchamp, J. N. Leffler, and E. E. Birch, “Binocular iPad game vs patching for treatment of amblyopia in children: a randomized clinical trial,” JAMA Ophthalmology, vol. 134, no. 12, pp. 1402–1408, 2016. View at Publisher · View at Google Scholar · View at Scopus
  36. S. L. Li, A. Reynaud, R. F. Hess et al., “Dichoptic movie viewing treats childhood amblyopia,” Journal of American Association for Pediatric Ophthalmology and Strabismus, vol. 19, no. 5, pp. 401–405, 2015. View at Publisher · View at Google Scholar · View at Scopus
  37. K. R. Kelly, R. M. Jost, Y.-Z. Wang et al., “Improved binocular outcomes following binocular treatment for childhood amblyopia,” Investigative Opthalmology & Visual Science, vol. 59, no. 3, pp. 1221–1228, 2018. View at Publisher · View at Google Scholar · View at Scopus
  38. R. W. Li, C. Ngo, J. Nguyen, and D. M. Levi, “Video-game play induces plasticity in the visual system of adults with amblyopia,” PLoS Biology, vol. 9, no. 8, article e1001135, 2011. View at Publisher · View at Google Scholar · View at Scopus
  39. D. Mezad-Koursh, A. Rosenblatt, H. Newman, and C. Stolovitch, “Home use of binocular dichoptic video content device for treatment of amblyopia: a pilot study,” Journal of American Association for Pediatric Ophthalmology and Strabismus, vol. 22, no. 2, pp. 134–138.e4, 2018. View at Publisher · View at Google Scholar · View at Scopus
  40. M. Bossi, V. K. Tailor, E. J. Anderson et al., “Binocular therapy for childhood amblyopia improves vision without breaking interocular suppression,” Investigative Ophthalmology & Visual Science, vol. 58, no. 7, pp. 3031–3043, 2017. View at Publisher · View at Google Scholar · View at Scopus
  41. B. Dong, Y. Jiang, S. A. Engel, and M. Bao, “Adaptation to patch-wise complementary video reduces perceptual ocular dominance,” Journal of Vision, vol. 14, no. 10, 2014. View at Publisher · View at Google Scholar
  42. C. Gambacorta, M. Nahum, I. Vedamurthy et al., “An action video game for the treatment of amblyopia in children: a feasibility study,” Vision Research, vol. 148, pp. 1–14, 2018. View at Publisher · View at Google Scholar · View at Scopus
  43. R. F. Hess, B. Thompson, J. M. Black et al., “An iPod treatment of amblyopia: an updated binocular approach,” Optometry, vol. 83, no. 2, pp. 87–94, 2012. View at Google Scholar
  44. S. L. Li, R. M. Jost, S. E. Morale et al., “Binocular iPad treatment of amblyopia for lasting improvement of visual acuity,” JAMA Ophthalmology, vol. 133, no. 4, pp. 479-480, 2015. View at Publisher · View at Google Scholar · View at Scopus
  45. S. Noah, J. Bayliss, I. Vedamurthy, M. Nahum, D. Levi, and D. Bavelier, “Comparing dichoptic action video game play to patching in adults with amblyopia,” Journal of Vision, vol. 14, no. 10, p. 691, 2014. View at Publisher · View at Google Scholar
  46. P. E. Waddingham, T. K. H. Butler, S. V. Cobb et al., “Preliminary results from the use of the novel interactive binocular treatment (I-BiT) system, in the treatment of strabismic and anisometropic amblyopia,” Eye, vol. 20, no. 3, pp. 375–378, 2006. View at Publisher · View at Google Scholar · View at Scopus
  47. S. T. Jeon, D. Maurer, and T. L. Lewis, “The effect of video game training on the vision of adults with bilateral deprivation amblyopia,” Seeing and Perceiving, vol. 25, no. 5, pp. 493–520, 2012. View at Publisher · View at Google Scholar · View at Scopus
  48. C. Lunghi, D. C. Burr, and C. Morrone, “Brief periods of monocular deprivation disrupt ocular balance in human adult visual cortex,” Current Biology, vol. 21, no. 14, pp. R538–R539, 2011. View at Publisher · View at Google Scholar · View at Scopus
  49. E. Chadnova, A. Reynaud, S. Clavagnier, and R. F. Hess, “Short-term monocular occlusion produces changes in ocular dominance by a reciprocal modulation of interocular inhibition,” Scientific Reports, vol. 7, no. 1, article 41747, 2017. View at Publisher · View at Google Scholar · View at Scopus
  50. J. Zhou, S. Clavagnier, and R. F. Hess, “Short-term monocular deprivation strengthens the patched eye’s contribution to binocular combination,” Journal of Vision, vol. 13, no. 5, 2013. View at Publisher · View at Google Scholar · View at Scopus
  51. C. Lunghi, D. C. Burr, and M. C. Morrone, “Long-term effects of monocular deprivation revealed with binocular rivalry gratings modulated in luminance and in color,” Journal of Vision, vol. 13, no. 6, p. 1, 2013. View at Publisher · View at Google Scholar · View at Scopus
  52. J. Zhou, B. Thompson, and R. F. Hess, “A new form of rapid binocular plasticity in adult with amblyopia,” Scientific Reports, vol. 3, no. 1, article 2638, 2013. View at Publisher · View at Google Scholar · View at Scopus
  53. J. Zhou, A. Reynaud, and R. F. Hess, “Real-time modulation of perceptual eye dominance in humans,” Proceedings of the Royal Society B: Biological Sciences, vol. 281, no. 1795, article 20141717, 2014. View at Publisher · View at Google Scholar · View at Scopus
  54. T. K. Hensch and M. Fagiolini, “Excitatory-inhibitory balance and critical period plasticity in developing visual cortex,” Progress in Brain Research, vol. 147, pp. 115–124, 2005. View at Publisher · View at Google Scholar · View at Scopus
  55. E. Zohary, S. Celebrini, K. H. Britten, and W. T. Newsome, “Neuronal plasticity that underlies improvement in perceptual performance,” Science, vol. 263, no. 5151, pp. 1289–1292, 1994. View at Publisher · View at Google Scholar · View at Scopus
  56. T. H. Brown, E. W. Kairiss, and C. L. Keenan, “Hebbian synapses: biophysical mechanisms and algorithms,” Annual Review of Neuroscience, vol. 13, no. 1, pp. 475–511, 1990. View at Publisher · View at Google Scholar · View at Scopus
  57. L. A. Lesmes, Z.-L. Lu, J. Baek, and T. D. Albright, “Bayesian adaptive estimation of the contrast sensitivity function: the quick CSF method,” Journal of Vision, vol. 17, no. 3, pp. 1–21, 2010. View at Publisher · View at Google Scholar · View at Scopus
  58. F. Hou, C.-B. Huang, L. Lesmes et al., “qCSF in clinical application: efficient characterization and classification of contrast sensitivity functions in amblyopia,” Investigative Opthalmology & Visual Science, vol. 51, no. 10, pp. 5365–5377, 2010. View at Publisher · View at Google Scholar · View at Scopus
  59. Y. Gao, A. Reynaud, Y. Tang, L. Feng, Y. Zhou, and R. F. Hess, “The amblyopic deficit for 2nd order processing: generality and laterality,” Vision Research, vol. 114, pp. 111–121, 2015. View at Publisher · View at Google Scholar · View at Scopus
  60. A. Reynaud, Y. Tang, Y. Zhou, and R. F. Hess, “A normative framework for the study of second-order sensitivity in vision,” Journal of Vision, vol. 14, no. 9, 2014. View at Publisher · View at Google Scholar · View at Scopus
  61. M. Kwon, E. Wiecek, S. C. Dakin, and P. J. Bex, “Spatial-frequency dependent binocular imbalance in amblyopia,” Scientific Reports, vol. 5, no. 1, article 17181, 2015. View at Publisher · View at Google Scholar · View at Scopus
  62. E. E. Birch, S. E. Morale, R. M. Jost et al., “Assessing suppression in amblyopic children with a dichoptic eye chart,” Investigative Ophthalmology & Visual Science, vol. 57, no. 13, pp. 5649–5654, 2016. View at Publisher · View at Google Scholar · View at Scopus
  63. B. Julesz, “Stereoscopic vision,” Vision Research, vol. 26, no. 9, pp. 1601–1612, 1986. View at Publisher · View at Google Scholar · View at Scopus
  64. J. M. Holmes and D. M. Levi, “Treatment of amblyopia as a function of age,” Visual Neuroscience, vol. 35, article E015, 2018. View at Publisher · View at Google Scholar · View at Scopus
  65. D. M. Levi, D. C. Knill, and D. Bavelier, “Stereopsis and amblyopia: a mini-review,” Vision Research, vol. 114, pp. 17–30, 2015. View at Publisher · View at Google Scholar · View at Scopus
  66. A. Reynaud and R. F. Hess, “Interocular correlation sensitivity and its relationship with stereopsis,” Journal of Vision, vol. 18, no. 1, p. 11, 2018. View at Publisher · View at Google Scholar · View at Scopus
  67. R. W. Li, K. So, T. H. Wu et al., “Monocular blur alters the tuning characteristics of stereopsis for spatial frequency and size,” Royal Society Open Science, vol. 3, no. 9, article 160273, 2016. View at Publisher · View at Google Scholar · View at Scopus
  68. J. Tittes, A. S. Baldwin, R. F. Hess et al., “Digital or analogue? First assessment of a newly developed digital stereotest in adults and children with and without amblyopia,” in European Conference on Visual Perception, Trieste, 2018.
  69. J. M. Holmes, V. M. Manh, E. L. Lazar et al., “Effect of a binocular iPad game vs part-time patching in children aged 5 to 12 years with amblyopia: a randomized clinical trial,” JAMA Ophthalmology, vol. 134, no. 12, pp. 1391–1400, 2016. View at Publisher · View at Google Scholar · View at Scopus
  70. J. Wang, “Compliance and patching and atropine amblyopia treatments,” Vision Research, vol. 114, pp. 31–40, 2015. View at Publisher · View at Google Scholar · View at Scopus
  71. W. Wen, X. Sun, H. Liu, and X. Li, “A dichoptic augmented-reality paradigm as a treatment for adult amblyopes,” Investigative Ophthalmology & Visual Science, vol. 58, no. 8, article 3829, 2017. View at Google Scholar
  72. A. D. Deemer, C. K. Bradley, N. C. Ross et al., “Low vision enhancement with head-mounted video display systems: are we there yet?” Optometry and Vision Science, vol. 95, no. 9, pp. 694–703, 2018. View at Publisher · View at Google Scholar · View at Scopus
  73. M. Falconbridge, D. Wozny, L. Shams, and S. A. Engel, “Adapting to altered image statistics using processed video,” Vision Research, vol. 49, no. 14, pp. 1757–1764, 2009. View at Publisher · View at Google Scholar · View at Scopus
  74. P. Zhang, M. Bao, M. Kwon, S. He, and S. A. Engel, “Effects of orientation-specific visual deprivation induced with altered reality,” Current Biology, vol. 19, no. 22, pp. 1956–1960, 2009. View at Publisher · View at Google Scholar · View at Scopus
  75. G. C. DeAngelis, A. Anzai, I. Ohzawa, and R. D. Freeman, “Receptive field structure in the visual cortex: does selective stimulation induce plasticity?” Proceedings of the National Academy of Sciences of the United States of America, vol. 92, no. 21, pp. 9682–9686, 1995. View at Publisher · View at Google Scholar · View at Scopus
  76. B. Boroojerdi, F. Battaglia, W. Muellbacher, and L. G. Cohen, “Mechanisms underlying rapid experience-dependent plasticity in the human visual cortex,” Proceedings of the National Academy of Sciences, vol. 98, no. 25, pp. 14698–14701, 2001. View at Publisher · View at Google Scholar · View at Scopus
  77. C. Lunghi, A. T. Sframeli, A. Lepri et al., “A new counterintuitive training for adult amblyopia,” Annals of Clinical and Translational Neurology, vol. 6, no. 2, pp. 274–284, 2018. View at Publisher · View at Google Scholar · View at Scopus
  78. J. Zhou, Z. He, Y. Wu et al., “Inverse occlusion: a binocularly motivated treatment for amblyopia,” Neural Plasticity, vol. 2019, Article ID 5157628, 12 pages, 2019. View at Publisher · View at Google Scholar
  79. A. Karni and D. Sagi, “The time course of learning a visual skill,” Nature, vol. 365, no. 6443, pp. 250–252, 1993. View at Publisher · View at Google Scholar · View at Scopus
  80. F. Sengpiel, “Plasticity of the visual cortex and treatment of amblyopia,” Current Biology, vol. 24, no. 18, pp. R936–R940, 2014. View at Publisher · View at Google Scholar · View at Scopus
  81. M. Scali, L. Baroncelli, M. C. Cenni, A. Sale, and L. Maffei, “A rich environmental experience reactivates visual cortex plasticity in aged rats,” Experimental Gerontology, vol. 47, no. 4, pp. 337–341, 2012. View at Publisher · View at Google Scholar · View at Scopus
  82. L. Baroncelli, A. Sale, A. Viegi et al., “Experience-dependent reactivation of ocular dominance plasticity in the adult visual cortex,” Experimental Neurology, vol. 226, no. 1, pp. 100–109, 2010. View at Publisher · View at Google Scholar · View at Scopus