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1.  Perceptual Learning Reduces Crowding in Amblyopia and in the Normal Periphery 
Amblyopia is a developmental visual disorder of cortical origin, characterized by crowding and poor acuity in central vision of the affected eye. Crowding refers to the adverse effects of surrounding items on object identification, common only in normal peripheral but not central vision. We trained a group of adult human amblyopes on a crowded letter identification task to assess whether the crowding problem can be ameliorated. Letter size was fixed well above the acuity limit, and letter spacing was varied to obtain spacing thresholds for central target identification. Normally sighted observers practiced the same task in their lower peripheral visual field. Independent measures of acuity were taken in flanked and unflanked conditions before and after training to measure crowding ratios at three fixed letter separations. Practice improved the letter spacing thresholds of both groups on the training task, and crowding ratios were reduced after posttest. The reductions in crowding in amblyopes were associated with improvements in standard measures of visual acuity. Thus, perceptual learning reduced the deleterious effects of crowding in amblyopia and in the normal periphery. The results support the effectiveness of plasticity-based approaches for improving vision in adult amblyopes and suggest experience-dependent effects on the cortical substrates of crowding.
doi:10.1523/JNEUROSCI.3845-11.2012
PMCID: PMC3428833  PMID: 22238083
2.  A double dissociation of the acuity and crowding limits to letter identification, and the promise of improved visual screening 
Journal of Vision  2014;14(5):3.
Here, we systematically explore the size and spacing requirements for identifying a letter among other letters. We measure acuity for flanked and unflanked letters, centrally and peripherally, in normals and amblyopes. We find that acuity, overlap masking, and crowding each demand a minimum size or spacing for readable text. Just measuring flanked and unflanked acuity is enough for our proposed model to predict the observer's threshold size and spacing for letters at any eccentricity.
We also find that amblyopia in adults retains the character of the childhood condition that caused it. Amblyopia is a developmental neural deficit that can occur as a result of either strabismus or anisometropia in childhood. Peripheral viewing during childhood due to strabismus results in amblyopia that is crowding limited, like peripheral vision. Optical blur of one eye during childhood due to anisometropia without strabismus results in amblyopia that is acuity limited, like blurred vision. Furthermore, we find that the spacing:acuity ratio of flanked and unflanked acuity can distinguish strabismic amblyopia from purely anisometropic amblyopia in nearly perfect agreement with lack of stereopsis. A scatter diagram of threshold spacing versus acuity, one point per patient, for several diagnostic groups, reveals the diagnostic power of flanked acuity testing. These results and two demonstrations indicate that the sensitivity of visual screening tests can be improved by using flankers that are more tightly spaced and letter like.
Finally, in concert with Strappini, Pelli, Di Pace, and Martelli (submitted), we jointly report a double dissociation between acuity and crowding. Two clinical conditions—anisometropic amblyopia and apperceptive agnosia—each selectively impair either acuity A or the spacing:acuity ratio S/A, not both. Furthermore, when we specifically estimate crowding, we find a double dissociation between acuity and crowding. Models of human object recognition will need to accommodate this newly discovered independence of acuity and crowding.
doi:10.1167/14.5.3
PMCID: PMC4021854  PMID: 24799622
amblyopia; crowding; strabismic; anisometropic; acuity; screening; spacing:acuity ratio; critical spacing; threshold spacing; legibility; overlap masking; letter identification; object recognition
3.  Reducing Crowding by Weakening Inhibitory Lateral Interactions in the Periphery with Perceptual Learning 
PLoS ONE  2011;6(10):e25568.
We investigated whether lateral masking in the near-periphery, due to inhibitory lateral interactions at an early level of central visual processing, could be weakened by perceptual learning and whether learning transferred to an untrained, higher-level lateral masking known as crowding. The trained task was contrast detection of a Gabor target presented in the near periphery (4°) in the presence of co-oriented and co-aligned high contrast Gabor flankers, which featured different target-to-flankers separations along the vertical axis that varied from 2λ to 8λ. We found both suppressive and facilitatory lateral interactions at target-to-flankers distances (2λ - 4λ and 8λ, respectively) that were larger than those found in the fovea. Training reduces suppression but does not increase facilitation. Most importantly, we found that learning reduces crowding and improves contrast sensitivity, but has no effect on visual acuity (VA). These results suggest a different pattern of connectivity in the periphery with respect to the fovea as well as a different modulation of this connectivity via perceptual learning that not only reduces low-level lateral masking but also reduces crowding. These results have important implications for the rehabilitation of low-vision patients who must use peripheral vision to perform tasks, such as reading and refined figure-ground segmentation, which normal sighted subjects perform in the fovea.
doi:10.1371/journal.pone.0025568
PMCID: PMC3204963  PMID: 22065990
4.  Video-Game Play Induces Plasticity in the Visual System of Adults with Amblyopia 
PLoS Biology  2011;9(8):e1001135.
A pilot study suggests that playing video games may enhance a range of spatial vision functions in adults with amblyopia.
Abnormal visual experience during a sensitive period of development disrupts neuronal circuitry in the visual cortex and results in abnormal spatial vision or amblyopia. Here we examined whether playing video games can induce plasticity in the visual system of adults with amblyopia. Specifically 20 adults with amblyopia (age 15–61 y; visual acuity: 20/25–20/480, with no manifest ocular disease or nystagmus) were recruited and allocated into three intervention groups: action videogame group (n = 10), non-action videogame group (n = 3), and crossover control group (n = 7). Our experiments show that playing video games (both action and non-action games) for a short period of time (40–80 h, 2 h/d) using the amblyopic eye results in a substantial improvement in a wide range of fundamental visual functions, from low-level to high-level, including visual acuity (33%), positional acuity (16%), spatial attention (37%), and stereopsis (54%). Using a cross-over experimental design (first 20 h: occlusion therapy, and the next 40 h: videogame therapy), we can conclude that the improvement cannot be explained simply by eye patching alone. We quantified the limits and the time course of visual plasticity induced by video-game experience. The recovery in visual acuity that we observed is at least 5-fold faster than would be expected from occlusion therapy in childhood amblyopia. We used positional noise and modelling to reveal the neural mechanisms underlying the visual improvements in terms of decreased spatial distortion (7%) and increased processing efficiency (33%). Our study had several limitations: small sample size, lack of randomization, and differences in numbers between groups. A large-scale randomized clinical study is needed to confirm the therapeutic value of video-game treatment in clinical situations. Nonetheless, taken as a pilot study, this work suggests that video-game play may provide important principles for treating amblyopia, and perhaps other cortical dysfunctions.
Trial Registration
ClinicalTrials.gov NCT01223716
Author Summary
Early abnormal visual experience disrupts neuronal circuitry in the brain and results in reduced vision, known as amblyopia or “lazy eye,” the most frequent cause of permanent visual loss in childhood. It is generally believed that adult amblyopia is irreversible beyond the sensitive period of brain development during childhood. In this study, we examine whether playing video games, both action and non-action, has an effect on the vision of adults with amblyopia. We assessed visual acuity (visual resolution), positional acuity (the ability to localize object's relative position), spatial attention (the ability to direct visual attention to various locations in the visual field), and stereoacuity (stereo-vision / 3-D depth perception) in a small group of teenagers and adults. We found that they tended to recover vision much faster than we would have expected from the results of conventional occlusion therapy in childhood amblyopia. Additional experiments and modelling suggest that the improvements are a result of decreasing spatial distortion and increasing information processing efficiency in the amblyopic brain. Thus, video games may include essential elements for active vision training to boost visual performance. Most importantly, our findings suggest that video-game play may provide important principles for treating amblyopia, a suggestion that we are pursuing with larger scale clinical trials.
doi:10.1371/journal.pbio.1001135
PMCID: PMC3166159  PMID: 21912514
5.  Training improves visual processing speed and generalizes to untrained functions 
Scientific Reports  2014;4:7251.
Studies show that manipulating certain training features in perceptual learning determines the specificity of the improvement. The improvement in abnormal visual processing following training and its generalization to visual acuity, as measured on static clinical charts, can be explained by improved sensitivity or processing speed. Crowding, the inability to recognize objects in a clutter, fundamentally limits conscious visual perception. Although it was largely considered absent in the fovea, earlier studies report foveal crowding upon very brief exposures or following spatial manipulations. Here we used GlassesOff's application for iDevices to train foveal vision of young participants. The training was performed at reading distance based on contrast detection tasks under different spatial and temporal constraints using Gabor patches aimed at testing improvement of processing speed. We found several significant improvements in spatio-temporal visual functions including near and also non-trained far distances. A remarkable transfer to visual acuity measured under crowded conditions resulted in reduced processing time of 81 ms, in order to achieve 6/6 acuity. Despite a subtle change in contrast sensitivity, a robust increase in processing speed was found. Thus, enhanced processing speed may lead to overcoming foveal crowding and might be the enabling factor for generalization to other visual functions.
doi:10.1038/srep07251
PMCID: PMC4246693  PMID: 25431233
6.  Identification of contrast-defined letters benefits from perceptual learning in adults with amblyopia 
Vision research  2006;46(22):3853-3861.
Amblyopes show specific deficits in processing second-order spatial information (e.g. Wong, Levi, & McGraw (2001). Is second-order spatial loss in amblyopia explained by the loss of first-order spatial input? Vision Research, 41, 2951–2960). Recent work suggests there is a significant degree of plasticity in the visual pathway that processes first-order spatial information in adults with amblyopia. In this study, we asked whether or not there is similar plasticity in the ability to process second-order spatial information in adults with amblyopia. Ten adult observers with amblyopia (five strabismic, four anisometropic and one mixed) were trained to identify contrast-defined (second-order) letters using their amblyopic eyes. Before and after training, we determined observers’ contrast thresholds for identifying luminance-defined (first-order) and contrast-defined letters, separately for the non-amblyopic and amblyopic eyes. Following training, eight of the 10 observers showed a significant reduction in contrast thresholds for identifying contrast-defined letters with the amblyopic eye. Five of these observers also showed a partial transfer of improvement to their fellow untrained non-amblyopic eye for identifying contrast-defined letters. There was a small but statistically significant transfer to the untrained task of identifying luminance-defined letters in the same trained eye. Similar to first-order spatial tasks, adults with amblyopia benefit from perceptual learning for identifying contrast-defined letters in their amblyopic eyes, suggesting a sizeable degree of plasticity in the visual pathway for processing second-order spatial information.
doi:10.1016/j.visres.2006.06.014
PMCID: PMC1852540  PMID: 16930666
Amblyopia; Letter recognition; Perceptual learning; Second-order
7.  The Pattern of Learned Visual Improvements in Adult Amblyopia 
The pattern of learned improvements in adult amblyopia was mapped onto a two-dimensional (sensitivity-acuity) deficit space. This approach enabled the identification of tasks and stimulus configurations that optimize learning.
Purpose.
Although amblyopia is diagnosed in terms of a monocular letter acuity loss, individuals typically present with deficits on a wide range of spatial tasks. Many of these deficits can be collapsed along two basic visual dimensions (visual acuity and contrast sensitivity) that together account for most of the variability in performance of the amblyopic visual system. In this study, this space was exploited, to target the main deficits and fully characterize the pattern of learned visual improvements in adult amblyopic subjects.
Methods.
Twenty-six amblyopic subjects (mean age, 39 ±12 years) were trained on one of four tasks, categorized as either visual acuity (letter or grating acuity) or contrast sensitivity (letter or grating contrast) tasks. Performance was measured on all tasks before and after training, to quantify learning along each dimension and generalization to the other dimension. Performance in 35 visually normal subjects (mean, age 24 ± 5 years) was used to establish normal variation in visual performance along each dimension, against which the learned improvements in amblyopic subjects was compared.
Results.
Training on the contrast sensitivity tasks produced substantial within-task learning and generalization to measures of visual acuity. The learned improvements in performance after training on the letter acuity task were also substantial, but did not generalize to contrast sensitivity.
Conclusions.
Mapping the pattern of learning onto the known deficit space for amblyopia enabled the identification of tasks and stimulus configurations that optimized learning, guiding further development of learning-based interventions in this clinical group.
doi:10.1167/iovs.11-7584
PMCID: PMC3207721  PMID: 21810976
8.  Perceptual Learning Improves Adult Amblyopic Vision Through Rule-Based Cognitive Compensation 
Purpose.
We investigated whether perceptual learning in adults with amblyopia could be enabled to transfer completely to an orthogonal orientation, which would suggest that amblyopic perceptual learning results mainly from high-level cognitive compensation, rather than plasticity in the amblyopic early visual brain.
Methods.
Nineteen adults (mean age = 22.5 years) with anisometropic and/or strabismic amblyopia were trained following a training-plus-exposure (TPE) protocol. The amblyopic eyes practiced contrast, orientation, or Vernier discrimination at one orientation for six to eight sessions. Then the amblyopic or nonamblyopic eyes were exposed to an orthogonal orientation via practicing an irrelevant task. Training was first performed at a lower spatial frequency (SF), then at a higher SF near the cutoff frequency of the amblyopic eye.
Results.
Perceptual learning was initially orientation specific. However, after exposure to the orthogonal orientation, learning transferred to an orthogonal orientation completely. Reversing the exposure and training order failed to produce transfer. Initial lower SF training led to broad improvement of contrast sensitivity, and later higher SF training led to more specific improvement at high SFs. Training improved visual acuity by 1.5 to 1.6 lines (P < 0.001) in the amblyopic eyes with computerized tests and a clinical E acuity chart. It also improved stereoacuity by 53% (P < 0.001).
Conclusions.
The complete transfer of learning suggests that perceptual learning in amblyopia may reflect high-level learning of rules for performing a visual discrimination task. These rules are applicable to new orientations to enable learning transfer. Therefore, perceptual learning may improve amblyopic vision mainly through rule-based cognitive compensation.
Amblyopic perceptual learning is cognitive compensation.
doi:10.1167/iovs.13-13739
PMCID: PMC3974581  PMID: 24550359
amblyopia; perceptual learning; orientation
9.  Training in Contrast Detection Improves Motion Perception of Sinewave Gratings in Amblyopia 
In this study, training in spatial vision led to improvements in motion perception of sinewave gratings in amblyopia. The results provide new empirical support for perceptual learning as a potential treatment for amblyopia.
Purpose.
One critical concern about using perceptual learning to treat amblyopia is whether training with one particular stimulus and task generalizes to other stimuli and tasks. In the spatial domain, it has been found that the bandwidth of contrast sensitivity improvement is much broader in amblyopes than in normals. Because previous studies suggested the local motion deficits in amblyopia are explained by the spatial vision deficits, the hypothesis for this study was that training in the spatial domain could benefit motion perception of sinewave gratings.
Methods.
Nine adult amblyopes (mean age, 22.1 ± 5.6 years) were trained in a contrast detection task in the amblyopic eye for 10 days. Visual acuity, spatial contrast sensitivity functions, and temporal modulation transfer functions (MTF) for sinewave motion detection and discrimination were measured for each eye before and after training. Eight adult amblyopes (mean age, 22.6 ± 6.7 years) served as control subjects.
Results.
In the amblyopic eye, training improved (1) contrast sensitivity by 6.6 dB (or 113.8%) across spatial frequencies, with a bandwidth of 4.4 octaves; (2) sensitivity of motion detection and discrimination by 3.2 dB (or 44.5%) and 3.7 dB (or 53.1%) across temporal frequencies, with bandwidths of 3.9 and 3.1 octaves, respectively; (3) visual acuity by 3.2 dB (or 44.5%). The fellow eye also showed a small amount of improvement in contrast sensitivities and no significant change in motion perception. Control subjects who received no training demonstrated no obvious improvement in any measure.
Conclusions.
The results demonstrate substantial plasticity in the amblyopic visual system, and provide additional empirical support for perceptual learning as a potential treatment for amblyopia.
doi:10.1167/iovs.11-7541
PMCID: PMC3176008  PMID: 21693615
10.  The Effect of Aging on Crowded Letter Recognition in the Peripheral Visual Field 
Purpose.
Crowding describes the increased difficulty in identifying a target object when it is surrounded by nearby objects (flankers). A recent study investigated the effect of age on visual crowding and found equivocal results: Although crowded visual acuity was worse in older participants, crowding expressed as a ratio did not change with age. However, the spatial extent of crowding is a better index of crowding effects and remains unknown. In the present study, we used established psychophysical methods to characterize the effect of age on visual crowding (magnitude and extent) in a letter recognition task.
Methods.
Letter recognition thresholds were determined for three different flanker separations in 54 adults (aged 18–76 years) with normal vision. Additionally, the spatial extent of crowding was established by measuring spacing thresholds: the flanker-to-target separation required to produce a given reduction in performance. Uncrowded visual acuity, crowded visual acuity, and spacing thresholds were expressed as a function of age, avoiding arbitrary categorization of young and old participants.
Results.
Our results showed that uncrowded and crowded visual acuities do not change significantly as a function of age. Furthermore, spacing thresholds did not change with age and approximated Bouma's law (half eccentricity).
Conclusions.
These data show that crowding in adults is unaffected by senescence and provide additional evidence for distinct neural mechanisms mediating surround suppression and visual crowding, since the former shows a significant age effect. Finally, our data suggest that the well-documented age-related decline in peripheral reading ability is not due to age-related changes in visual crowding.
Crowding for a peripheral letter recognition task was measured as a function of age. Both the magnitude and spatial extent of crowding did not change with age. The results have important implications for the visual rehabilitation of patients with central vision loss.
doi:10.1167/iovs.14-14181
PMCID: PMC4132554  PMID: 24985476
crowding; aging; visual acuity; critical spacing; reading
11.  Context and Crowding in Perceptual Learning on a Peripheral Contrast Discrimination Task: Context-Specificity in Contrast Learning 
PLoS ONE  2013;8(5):e63278.
Perceptual learning is an improvement in sensitivity due to practice on a sensory task and is generally specific to the trained stimuli and/or tasks. The present study investigated the effect of stimulus configuration and crowding on perceptual learning in contrast discrimination in peripheral vision, and the effect of perceptual training on crowding in this task. 29 normally-sighted observers were trained to discriminate Gabor stimuli presented at 9° eccentricity with either identical or orthogonally oriented flankers with respect to the target (ISO and CROSS, respectively), or on an isolated target (CONTROL). Contrast discrimination thresholds were measured at various eccentricities and target-flanker separations before and after training in order to determine any learning transfer to untrained stimulus parameters. Perceptual learning was observed in all three training stimuli; however, greater improvement was obtained with training on ISO-oriented stimuli compared to CROSS-oriented and unflanked stimuli. This learning did not transfer to untrained stimulus configurations, eccentricities or target-flanker separations. A characteristic crowding effect was observed increasing with viewing eccentricity and decreasing with target-flanker separation before and after training in both configurations. The magnitude of crowding was reduced only at the trained eccentricity and target-flanker separation; therefore, learning for contrast discrimination and for crowding in the present study was configuration and location specific. Our findings suggest that stimulus configuration plays an important role in the magnitude of perceptual learning in contrast discrimination and suggest context-specificity in learning.
doi:10.1371/journal.pone.0063278
PMCID: PMC3655984  PMID: 23696807
12.  Learning to identify crowded letters: Does the learning depend on the frequency of training? 
Vision research  2012;77:41-50.
Performance for many visual tasks improves with training. The magnitude of improvement following training depends on the training task, number of trials per training session and the total amount of training. Does the magnitude of improvement also depend on the frequency of training sessions? In this study, we compared the learning effect for three groups of normally sighted observers who repeatedly practiced the task of identifying crowded letters in the periphery for six sessions (1000 trials per session), according to three different training schedules — one group received one session of training everyday, the second group received a training session once a week and the third group once every two weeks. Following six sessions of training, all observers improved in their performance of identifying crowded letters in the periphery. Most importantly, the magnitudes of improvement were similar across the three training groups. The improvement was accompanied by a reduction in the spatial extent of crowding, an increase in the size of visual span and a reduction in letter-size threshold. The magnitudes of these accompanied improvements were also similar across the three training groups. Our finding that the effectiveness of visual perceptual learning is similar for daily, weekly and biweekly training has significant implication for adopting perceptual learning as an option to improve visual functions for clinical patients.
doi:10.1016/j.visres.2012.11.009
PMCID: PMC3538889  PMID: 23206551
perceptual learning; crowding; letter identification; peripheral vision
13.  A systematic review on ‘Foveal Crowding’ in visually impaired children and perceptual learning as a method to reduce Crowding 
BMC Ophthalmology  2012;12:27.
Background
This systematic review gives an overview of foveal crowding (the inability to recognize objects due to surrounding nearby contours in foveal vision) and possible interventions. Foveal crowding can have a major effect on reading rate and deciphering small pieces of information from busy visual scenes. Three specific groups experience more foveal crowding than adults with normal vision (NV): 1) children with NV, 2) visually impaired (VI) children and adults and 3) children with cerebral visual impairment (CVI). The extent and magnitude of foveal crowding as well as interventions aimed at reducing crowding were investigated in this review. The twofold goal of this review is : [A] to compare foveal crowding in children with NV, VI children and adults and CVI children and [B] to compare interventions to reduce crowding.
Methods
Three electronic databases were used to conduct the literature search: PubMed, PsycINFO (Ovid), and Cochrane. Additional studies were identified by contacting experts. Search terms included visual perception, contour interaction, crowding, crowded, and contour interactions.
Results
Children with normal vision show an extent of contour interaction over an area 1.5–3× as large as that seen in adults NV. The magnitude of contour interaction normally ranges between 1–2 lines on an acuity chart and this magnitude is even larger when stimuli are arranged in a circular configuration. Adults with congenital nystagmus (CN) show interaction areas that are 2× larger than those seen adults with NV. The magnitude of the crowding effect is also 2× as large in individuals with CN as in individuals with NV. Finally, children with CVI experience a magnitude of the crowding effect that is 3× the size of that experienced by adults with NV.
Conclusions
The methodological heterogeneity, the diversity in paradigms used to measure crowding, made it impossible to conduct a meta-analysis. This is the first systematic review to compare crowding ratios and it shows that charts with 50% interoptotype spacing were most sensitive to capture crowding effects. The groups that showed the largest crowding effects were individuals with CN, VI adults with central scotomas and children with CVI. Perceptual Learning seems to be a promising technique to reduce excessive foveal crowding effects.
doi:10.1186/1471-2415-12-27
PMCID: PMC3416571  PMID: 22824242
14.  Amblyopia 
Clinical Evidence  2011;2011:0709.
Introduction
Amblyopia is commonly associated with squint (strabismus) or refractive errors resulting in different visual inputs to each eye during the sensitive period of visual development (<7–8 years of age). The cumulative incidence is estimated at 2% to 4% in children aged up to 15 years.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to detect amblyopia early? What are the effects of medical treatments for amblyopia? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations, such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 33 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: active vision therapy; glasses alone or with occlusion; or penalisation to treat amblyopia; and screening to detect amblyopia early.
Key Points
Amblyopia is reduced visual acuity not immediately correctable by glasses, in the absence of ocular pathology. It is commonly associated with squint (strabismic amblyopia), refractive errors resulting in different visual inputs to each eye during the sensitive period of visual development (refractive amblyopia), or with cataract or ptosis (stimulus deprivation amblyopia).The cumulative incidence is estimated at 2% to 4% in children aged up to 15 years.
Vision screening before school entry may increase detection rates of amblyopia. However, preschool screening may not improve treatment outcomes at 7 years compared with school-entry screening. We don't know whether children with a higher risk of eye problems should be targeted for vision screening.
Most evidence is available for children aged <7 years, in whom wearing glasses for up to 30 weeks can improve amblyopia and may cure it. Children with suspected amblyopia who have clinically important refractive error are prescribed glasses; therefore, most data available on other interventions assess their effectiveness in combination with glasses.
Occlusion (covering the fellow eye using a patch) may be more effective than glasses alone in children up to 13 years of age not fully treated with glasses. Further data assessing occlusion in combination with near-vision tasks, such as encouraging the child to do close work while wearing their patch, confirm that combined interventions are more effective than glasses alone in younger children. Some older children might improve with treatment, although there are few data available to support this.We don't know whether prescribing occlusion of the fellow eye for longer periods every day is more effective than prescribing for shorter periods of daily occlusion, but success rates do increase in proportion to objectively measured compliance. Penalisation with atropine may be as effective as occlusion when given in combination with other interventions for improving amblyopia in children aged <7 years who are not fully treated with glasses.We don't know whether near-vision tasks are effective alone as adjuvant treatment to glasses for amblyopia. Near-vision tasks may further enhance visual acuity when added to occlusion or penalisation, but the contribution of near-vision tasks to the effects of these combination interventions remains unclear.
PMCID: PMC3275294  PMID: 21714945
15.  Amblyopia 
Clinical Evidence  2009;2009:0709.
Introduction
Amblyopia is commonly associated with squint (strabismus) or refractive errors resulting in different visual inputs to each eye during the sensitive period of visual development (<7-8 years of age). The cumulative incidence is estimated at 2% to 4% in children aged up to 15 years.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to detect amblyopia early? What are the effects of medical treatments for amblyopia? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2008 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations, such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 16 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: active vision therapy; glasses alone or with occlusion; penalisation; screening; and targeted vision screening.
Key Points
Amblyopia is reduced visual acuity not immediately correctable by glasses, in the absence of ocular pathology. It is commonly associated with squint (strabismic amblyopia), refractive errors resulting in different visual inputs to each eye during the sensitive period of visual development (refractive amblyopia), or with cataract or ptosis (stimulus deprivation amblyopia).The cumulative incidence is estimated at 2% to 4% in children aged up to 15 years.
Vision screening before school entry may increase detection rates of amblyopia compared with no screening. However, pre-school screening may not improve treatment outcomes at 7 years compared with school-entry screening. We don't know whether children with a higher risk of eye problems should be targeted for vision screening.
Most evidence is available for children under 7 years of age, in whom wearing glasses for up to 30 weeks can improve amblyopia and may cure it. Children with suspected amblyopia who have clinically important refractive error are prescribed glasses; therefore most data available on other interventions assess their effectiveness in combination with glasses.
Occlusion (covering the fellow eye using a patch) may be more effective than glasses alone in children up to 13 years of age not fully treated with glasses. Further data assessing occlusion in combination with near-vision tasks such as encouraging the child to do close work while wearing their patch confirm that combined interventions are more effective than glasses alone in younger children. Some older children might improve with treatment, although there are few data available to support this.Prescribing occlusion for the fellow eye for longer periods every day is no more effective at improving amblyopia than prescribing shorter periods of daily occlusion, but success rates increase in proportion to objectively measured compliance. Penalisation with atropine may be as effective as occlusion when given in combination with other interventions for improving amblyopia in children aged under 7 years who are not fully treated with glasses.We don't know whether near-vision tasks are effective alone as adjuvant treatment to glasses for amblyopia. Near-vision tasks may further enhance visual acuity when added to occlusion or penalisation but the contribution of near-vision tasks to the effects of these combination interventions remains unclear.
PMCID: PMC2907781  PMID: 21726480
16.  Perceptual Learning as a potential treatment for amblyopia: a mini-review 
Vision research  2009;49(21):2535-2549.
Amblyopia is a developmental abnormality that results from physiological alterations in the visual cortex and impairs form vision. It is a consequence of abnormal binocular visual experience during the “sensitive period” early in life. While amblyopia can often be reversed when treated early, conventional treatment is generally not undertaken in older children and adults. A number of studies over the last twelve years or so suggest that Perceptual Learning (PL) may provide an important new method for treating amblyopia.
The aim of this mini-review is to provide a critical review and “meta-analysis” of perceptual learning in adults and children with amblyopia, with a view to extracting principles that might make PL more effective and efficient. Specifically we evaluate:
What factors influence the outcome of perceptual learning?Specificity and generalization – two sides of the coin.Do the improvements last?How does PL improve visual function?Should PL be part of the treatment armamentarium?
A review of the extant studies makes it clear that practicing a visual task results in a long-lasting improvement in performance in an amblyopic eye. The improvement is generally strongest for the trained eye, task, stimulus and orientation, but appears to have a broader spatial frequency bandwidth than in normal vision. Importantly, practicing on a variety of different tasks and stimuli seems to transfer to improved visual acuity. Perceptual learning operates via a reduction of internal neural noise and/or through more efficient use of the stimulus information by retuning the weighting of the information. The success of PL raises the question of whether it should become a standard part of the armamentarium for the clinical treatment of amblyopia, and suggests several important principles for effective perceptual learning in amblyopia.
doi:10.1016/j.visres.2009.02.010
PMCID: PMC2764839  PMID: 19250947
Amblyopia; perceptual learning; sensitive period; critical period; internal noise; template-retuning; occlusion
17.  Learning to Identify Crowded Letters: Does It Improve Reading Speed? 
Vision research  2007;47(25):3150-3159.
Crowding, the difficulty in identifying a letter embedded in other letters, has been suggested as an explanation for slow reading in peripheral vision. In this study, we asked whether crowding in peripheral vision can be reduced through training on identifying crowded letters, and if so, whether these changes will lead to improved peripheral reading speed. We measured the spatial extent of crowding, and reading speeds for a range of print sizes at 10° inferior visual field before and after training. Following training, averaged letter identification performance improved by 88% at the trained (the closest) letter separation. The improvement transferred to other untrained separations such that the spatial extent of crowding decreased by 38%. However, averaged maximum reading speed improved by a mere 7.2%. These findings demonstrated that crowding in peripheral vision could be reduced through training. Unfortunately, the reduction in the crowding effect did not lead to improved peripheral reading speed.
doi:10.1016/j.visres.2007.08.017
PMCID: PMC2134936  PMID: 17928026
crowding; perceptual learning; training; reading
18.  The nature of letter crowding as revealed by first- and second-order classification images 
Journal of vision  2007;7(2):5.1-526.
Visual crowding refers to the marked inability to identify an otherwise perfectly identifiable object when it is flanked by other objects. Crowding places a significant limit on form vision in the visual periphery; its mechanism is, however, unknown. Building on the method of signal-clamped classification images (Tjan & Nandy, 2006), we developed a series of first- and second-order classification-image techniques to investigate the nature of crowding without presupposing any model of crowding. Using an “o” versus “x” letter-identification task, we found that (1) crowding significantly reduced the contrast of first-order classification images, although it did not alter the shape of the classification images; (2) response errors during crowding were strongly correlated with the spatial structures of the flankers that resembled those of the erroneously perceived targets; (3) crowding had no systematic effect on intrinsic spatial uncertainty of an observer nor did it suppress feature detection; and (4) analysis of the second-order classification images revealed that crowding reduced the amount of valid features used by the visual system and, at the same time, increased the amount of invalid features used. Our findings strongly support the feature-mislocalization or source-confusion hypothesis as one of the proximal contributors of crowding. Our data also agree with the inappropriate feature-integration account with the requirement that feature integration be a competitive process. However, the feature-masking account and a front-end version of the spatial attention account of crowding are not supported by our data.
doi:10.1167/7.2.5
PMCID: PMC2635026  PMID: 18217820
crowding; letter identification; peripheral vision; classification images
19.  The challenges of developing a contrast-based video game for treatment of amblyopia 
Frontiers in Psychology  2014;5:1210.
Perceptual learning of visual tasks is emerging as a promising treatment for amblyopia, a developmental disorder of vision characterized by poor monocular visual acuity. The tasks tested thus far span the gamut from basic psychophysical discriminations to visually complex video games. One end of the spectrum offers precise control over stimulus parameters, whilst the other delivers the benefits of motivation and reward that sustain practice over long periods. Here, we combined the advantages of both approaches by developing a video game that trains contrast sensitivity, which in psychophysical experiments, is associated with significant improvements in visual acuity in amblyopia. Target contrast was varied adaptively in the game to derive a contrast threshold for each session. We tested the game on 20 amblyopic subjects (10 children and 10 adults), who played at home using their amblyopic eye for an average of 37 sessions (approximately 11 h). Contrast thresholds from the game improved reliably for adults but not for children. However, logMAR acuity improved for both groups (mean = 1.3 lines; range = 0–3.6 lines). We present the rationale leading to the development of the game and describe the challenges of incorporating psychophysical methods into game-like settings.
doi:10.3389/fpsyg.2014.01210
PMCID: PMC4217344  PMID: 25404922
anisometropia; binocular; contrast sensitivity; development; perceptual learning; strabismus; visual acuity
20.  Training-induced recovery of low-level vision followed by mid-level perceptual improvements in developmental object and face agnosia 
Developmental Science  2014;18(1):50-64.
Long-term deprivation of normal visual inputs can cause perceptual impairments at various levels of visual function, from basic visual acuity deficits, through mid-level deficits such as contour integration and motion coherence, to high-level face and object agnosia. Yet it is unclear whether training during adulthood, at a post-developmental stage of the adult visual system, can overcome such developmental impairments. Here, we visually trained LG, a developmental object and face agnosic individual. Prior to training, at the age of 20, LG's basic and mid-level visual functions such as visual acuity, crowding effects, and contour integration were underdeveloped relative to normal adult vision, corresponding to or poorer than those of 5–6 year olds (Gilaie-Dotan, Perry, Bonneh, Malach & Bentin, 2009). Intensive visual training, based on lateral interactions, was applied for a period of 9 months. LG's directly trained but also untrained visual functions such as visual acuity, crowding, binocular stereopsis and also mid-level contour integration improved significantly and reached near-age-level performance, with long-term (over 4 years) persistence. Moreover, mid-level functions that were tested post-training were found to be normal in LG. Some possible subtle improvement was observed in LG's higher-order visual functions such as object recognition and part integration, while LG's face perception skills have not improved thus far. These results suggest that corrective training at a post-developmental stage, even in the adult visual system, can prove effective, and its enduring effects are the basis for a revival of a developmental cascade that can lead to reduced perceptual impairments.
doi:10.1111/desc.12178
PMCID: PMC4309467  PMID: 24698161
21.  Improving visual functions in adult amblyopia with combined perceptual training and transcranial random noise stimulation (tRNS): a pilot study 
Frontiers in Psychology  2014;5:1402.
Amblyopia is a visual disorder due to an abnormal pattern of functional connectivity of the visual cortex and characterized by several visual deficits of spatial vision including impairments of visual acuity (VA) and of the contrast sensitivity function (CSF). Despite being a developmental disorder caused by reduced visual stimulation during early life (critical period), several studies have shown that extensive visual perceptual training can improve VA and CSF in people with amblyopia even in adulthood. With the present study we assessed whether a much shorter perceptual training regime, in association with high-frequency transcranial electrical stimulation (hf-tRNS), was able to improve visual functions in a group of adult participants with amblyopia. Results show that, in comparison with previous studies where a large number sessions with a similar training regime were used (Polat et al., 2004), here just eight sessions of training in contrast detection under lateral masking conditions combined with hf-tRNS, were able to substantially improve VA and CSF in adults with amblyopia.
doi:10.3389/fpsyg.2014.01402
PMCID: PMC4260493  PMID: 25538653
amblyopia; visual acuity; contrast sensitivity; perceptual learning; lateral masking; tRNS
22.  Crowding follows the binding of relative position and orientation 
Journal of vision  2012;12(3):10.1167/12.3.18 18.
Crowding–the deleterious influence of clutter on object recognition–disrupts the identification of visual features as diverse as orientation, motion, and color. It is unclear whether this occurs via independent feature-specific crowding processes (preceding the feature binding process) or via a singular (late) mechanism tuned for combined features. To examine the relationship between feature binding and crowding, we measured interactions between the crowding of relative position and orientation. Stimuli were a target cross and two flanker crosses (each composed of two near-orthogonal lines), 15 degrees in the periphery. Observers judged either the orientation (clockwise/counterclockwise) of the near-horizontal target line, its position (up/down relative to the stimulus center), or both. For single-feature judgments, crowding affected position and orientation similarly: thresholds were elevated and responses biased in a manner suggesting that the target appeared more like the flankers. These effects were tuned for orientation, with near-orthogonal elements producing little crowding. This tuning allowed us to separate the predictions of independent (feature specific) and combined (singular) models: for an independent model, reduced crowding for one feature has no effect on crowding for other features, whereas a combined process affects either all features or none. When observers made conjoint judgments, a reduction of orientation crowding (by increasing target–flanker orientation differences) increased the rate of correct responses for both position and orientation, as predicted by our combined model. In contrast, our independent model incorrectly predicted a high rate of position errors, since the probability of positional crowding would be unaffected by changes in orientation. Thus, at least for these features, crowding is a singular process that affects bound position and orientation values in an all-or-none fashion.
doi:10.1167/12.3.18
PMCID: PMC3624616  PMID: 22438467
crowding; orientation; position; feature binding; peripheral visual field
23.  Perceptual Learning Improves Stereoacuity in Amblyopia 
Purpose.
Amblyopia is a developmental disorder that results in both monocular and binocular deficits. Although traditional treatment in clinical practice (i.e., refractive correction, or occlusion by patching and penalization of the fellow eye) is effective in restoring monocular visual acuity, there is little information on how binocular function, especially stereopsis, responds to traditional amblyopia treatment. We aim to evaluate the effects of perceptual learning on stereopsis in observers with amblyopia in the current study.
Methods.
Eleven observers (21.1 ± 5.1 years, six females) with anisometropic or ametropic amblyopia were trained to judge depth in 10 to 13 sessions. Red–green glasses were used to present three different texture anaglyphs with different disparities but a fixed exposure duration. Stereoacuity was assessed with the Fly Stereo Acuity Test and visual acuity was assessed with the Chinese Tumbling E Chart before and after training.
Results.
Averaged across observers, training significantly reduced disparity threshold from 776.7″ to 490.4″ (P < 0.01) and improved stereoacuity from 200.3″ to 81.6″ (P < 0.01). Interestingly, visual acuity also significantly improved from 0.44 to 0.35 logMAR (approximately 0.9 lines, P < 0.05) in the amblyopic eye after training. Moreover, the learning effects in two of the three retested observers were largely retained over a 5-month period.
Conclusions.
Perceptual learning is effective in improving stereo vision in observers with amblyopia. These results, together with previous evidence, suggest that structured monocular and binocular training might be necessary to fully recover degraded visual functions in amblyopia.
Chinese Abstract
Traditional treatment cannot fully normalize stereoacuity in amblyopia. This study identifies that perceptual learning is of potential in restoring stereoacuity in adults with anisometropic amblyopia.
doi:10.1167/iovs.13-12627
PMCID: PMC3989086  PMID: 24508791
perceptual learning; stereoacuity; amblyopia
24.  Can human amblyopia be treated in adulthood? 
Strabismus  2011;19(3):99-109.
Amblyopia is a common visual disorder that results in a spatial acuity deficit in the affected eye. Orthodox treatment is to occlude the unaffected eye for lengthy periods, largely determined by the severity of the visual deficit at diagnosis. Although this treatment is not without its problems (poor compliance, potential to reduce binocular function etc.) it is effective in many children with moderate to severe amblyopia. Diagnosis and initiation of treatment early in life are thought to be critical to the success of this form of therapy. Occlusion is rarely undertaken in older children (over 10 years old) as the visual benefits are considered to be marginal. Therefore, in subjects where occlusion is not effective or those missed by mass screening programmes there is no alternative therapy available later in life. More recently, burgeoning evidence has begun to reveal previously unrecognised levels of residual neural plasticity in the adult brain and scientists have developed new genetic, pharmacological and behavioural interventions to activate these latent mechanisms in order to harness their potential for visual recovery. Prominent amongst these is the concept of perceptual learning - the fact that repeatedly practicing a challenging visual task leads to substantial and enduring improvements in visual performance over time. In the normal visual system the improvements are highly specific to the attributes of the trained stimulus. However, in the amblyopic visual system learned improvements have been shown to generalize to novel tasks. In this paper we ask whether amblyopic deficits can be reduced in adulthood and explore the pattern of transfer of learned improvements. We also show that developing training protocols that target the deficit in stereo acuity allows the recovery of normal stereo function even in adulthood. This information will help guide further development of learning-based interventions in this clinical group.
doi:10.3109/09273972.2011.600420
PMCID: PMC3433677  PMID: 21870913
Amblyopia; perceptual learning; plasticity; visual acuity; contrast sensitivity; stereo acuity
25.  Using visual noise to characterize amblyopic letter identification 
Journal of vision  2004;4(10):904-920.
Amblyopia is a much-studied but poorly understood developmental visual disorder that reduces acuity, profoundly reducing contrast sensitivity for small targets. Here we use visual noise to probe the letter identification process and characterize its impairment by amblyopia. We apply five levels of analysis — threshold, threshold in noise, equivalent noise, optical MTF, and noise modeling — to obtain a two-factor model of the amblyopic deficit: substantially reduced efficiency for small letters and negligibly increased cortical noise. Cortical noise, expressed as an equivalent input noise, varies among amblyopes but is roughly 1.4× normal, as though only 1/1.4 the normal number of cortical spikes are devoted to the amblyopic eye. This raises threshold contrast for large letters by a factor of √1.4 = 1.2×, a negligible effect. All 16 amblyopic observers showed near-normal efficiency for large letters (> 4× acuity) and greatly reduced efficiency for small letters: 1/4 normal at 2× acuity and approaching 1/16 normal at acuity. Finding that the acuity loss represents a loss of efficiency rules out all models of amblyopia except those that predict the same sensitivity loss on blank and noisy backgrounds. One such model is the last-channel hypothesis, which supposes that the highest-spatial-frequency channels are missing, leaving the remaining highest-frequency channel struggling to identify the smallest letters. However, this hypothesis is rejected by critical band masking of letter identification, which shows that the channels used by the amblyopic eye have normal tuning for even the smallest letters. Finally, based on these results, we introduce a new “Dual Acuity” chart that promises to be a quick diagnostic test for amblyopia.
doi:10.1167/4.10.6
PMCID: PMC2751822  PMID: 15595894
amblyopia; noise; efficiency; cortical noise; Pelli-Levi Dual Acuity Chart

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