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... Thus, clinical treatment was often limited to young children. However, this view has been widely refuted (Kupfer, 1957;Levi & Polat, 1996;Levi, Polat & Hu, 1997;Holmes & Levi, 2018 and see below). Large scale randomized clinical trials show that treatment may be effective in older (13 to 17 years) children who have not been previously treated (Pediatric Eye Disease Investigator Group, 2005), and a substantial number of studies have shown significant and long-lasting effects of experimental treatments in adults. ...
... Finally, while these results suggest the limits of conventional treatment, a review of the literature makes it clear that improvement in adults can exceed the predictions of the function shown in Fig. 3. The open diamonds replot the remarkable results reported by Carl Kupfer (1957) from seven young adults with strabismic amblyopia, with initial acuity ranging from 20/70 to hand motion only, following 6 weeks of hospitalization during which they underwent complete, constant occlusion of the strong eye combined with intensive fixation training. [Note that the Kupfer study was not a randomized clinical trial, and therefore may have been subject to experimenter bias, placebo effects, etc.]. ...
... (after Holmes and Levi, 2018). Also shown here (red diamonds) are data from a small group of adult amblyopes who underwent intensive treatment (see text) from Kupfer, 1957. The red line is a fit to the mean PEDIG data. ...
... Indeed, it is often stated that humans with amblyopia cannot be treated beyond a certain age. However, a review of the literature suggests otherwise (Kupfer, 1957;Holmes and Levi, 2018 and see later). Clinical trials suggest that treatment may be just as effective in older (13-17 years), patients who have not been Fig. 2.2. ...
... First, as evident in Fig. 2.4, the average data do not capture the huge Holmes and Levi, 2018). Also shown here (red diamonds) are data from a small group of adult amblyopes who underwent intensive treatment (see text) from Kupfer (1957). ...
... Finally, while these results suggest the limits of conventional treatment, a review of the literature makes it clear that improvement in adults can exceed the predictions of the function shown in Fig. 2.4. The open diamonds replot the remarkable results reported by Kupfer (1957) from seven young adults with strabismic amblyopia, with initial acuity ranging from 20/70 to hand motion only, following 6 weeks of hospitalization during which they underwent complete, constant occlusion of the strong eye combined with intensive fixation training. ...
Amblyopia is a neurodevelopmental abnormality that results in physiological alterations in the visual pathways and impaired vision in one eye, less commonly in both. It reflects a broad range of neural, perceptual, oculomotor, and clinical abnormalities that can occur when normal visual development is disrupted early in life. Aside from refractive error, amblyopia is the most common cause of vision loss in infants and young children. It causes a constellation of perceptual deficits in the vision of the amblyopic eye, including a loss of visual acuity, position acuity, and contrast sensitivity, particularly at high spatial frequencies, as well as increased internal noise and prolonged manual and saccadic reaction times. There are also perceptual deficits in the strong eye, such as certain types of motion perception, reflecting altered neural responses and functional connectivity in visual cortex (Ho et al., 2005). Treatment in young children consists of correction of any refractive error and patching of the strong eye. Compliance with patching is challenging and a substantial proportion of amblyopic children fail to achieve normal acuity or stereopsis even after extended periods of treatment. There are a number of promising experimental treatments that may improve compliance and outcomes, such as the playing of action video games with the strong eye patched. Although there may be a sensitive period for optimal effects of treatment, there is evidence that amblyopic adults may still show some benefit of treatment. However, there is as yet no consensus on the treatment of adults with amblyopia.
... Thus, clinical treatment was often limited to young children. However, this view has been widely refuted (Kupfer, 1957;Levi & Polat, 1996;Levi, Polat & Hu, 1997;Holmes & Levi, 2018 and see below). Large scale randomized clinical trials show that treatment may be effective in older (13 to 17 years) children who have not been previously treated (Pediatric Eye Disease Investigator Group, 2005), and a substantial number of studies have shown significant and long-lasting effects of experimental treatments in adults. ...
... Finally, while these results suggest the limits of conventional treatment, a review of the literature makes it clear that improvement in adults can exceed the predictions of the function shown in Fig. 3. The open diamonds replot the remarkable results reported by Carl Kupfer (1957) from seven young adults with strabismic amblyopia, with initial acuity ranging from 20/70 to hand motion only, following 6 weeks of hospitalization during which they underwent complete, constant occlusion of the strong eye combined with intensive fixation training. [Note that the Kupfer study was not a randomized clinical trial, and therefore may have been subject to experimenter bias, placebo effects, etc.]. ...
... (after Holmes and Levi, 2018). Also shown here (red diamonds) are data from a small group of adult amblyopes who underwent intensive treatment (see text) from Kupfer, 1957. The red line is a fit to the mean PEDIG data. ...
Recent work has transformed our ideas about the neural mechanisms, behavioral consequences and effective therapies for amblyopia. Since the 1700′s, the clinical treatment for amblyopia has consisted of patching or penalizing the strong eye, to force the “lazy” amblyopic eye, to work. This treatment has generally been limited to infants and young children during a sensitive period of development. Over the last 20 years we have learned much about the nature and neural mechanisms underlying the loss of spatial and binocular vision in amblyopia, and that a degree of neural plasticity persists well beyond the sensitive period. Importantly, the last decade has seen a resurgence of research into new approaches to the treatment of amblyopia both in children and adults, which emphasize that monocular therapies may not be the most effective for the fundamentally binocular disorder that is amblyopia. These approaches include perceptual learning, video game play and binocular methods aimed at reducing inhibition of the amblyopic eye by the strong fellow eye, and enhancing binocular fusion and stereopsis. This review focuses on the what we’ve learned over the past 20 years or so, and will highlight both the successes of these new treatment approaches in labs around the world, and their failures in clinical trials. Reconciling these results raises important new questions that may help to focus future directions.
... A study by Carl Kupfer (1957) 25 , showed marked improvement in visual acuity in seven adult strabismica amblyopes, aged 18 to 22 years from hand movements (they could not even count fingers due to dense amblyopia) to 20/25 after four weeks of intensive therapy. The patients were hospitalized for four weeks, during which time they were given full-time occlusion therapy and fixation training. ...
... A study by Carl Kupfer (1957) 25 , showed marked improvement in visual acuity in seven adult strabismica amblyopes, aged 18 to 22 years from hand movements (they could not even count fingers due to dense amblyopia) to 20/25 after four weeks of intensive therapy. The patients were hospitalized for four weeks, during which time they were given full-time occlusion therapy and fixation training. ...
Objective: To find out how much visual improvement is possible in severe amblyopia using full-time occlusion therapy and if improvement is influenced by the patient’s age.
Methods: A trial of 115 consecutive cases with unilateral, severe amblyopia was conducted at a tertiary referral center from Jan 2010 to Oct 2012. Patients were divided into three age groups: 3-7 years (n= 38), 8-12 years (n=41), 13-35 years (n=36). After a complete ophthalmological examination by a single ophthalmologist, cases with organic visual loss were excluded; cases with previous part-time occlusion therapy that had failed were included in the study. Patients were given optimal refractive correction for a month, followed by full-time occlusion therapy along with near visual activities for 3-4 hours/day. The therapy was continued until maximum visual recovery was achieved (6/6 Snellen’s). Therapy was gradually reduced and stopped. Patients were followed-up regularly for the next 18 months.
Results: There was 100% success in the 3-7 year group, 92.68% in the 8-12 year group and 97.22% in the 13-35 year group.
Conclusion: Visual improvement is possible in almost all patients with severe amblyopia irrespective of their age with full-time occlusion therapy.
... Visual training as a potential therapy for amblyopia has been evaluated since the pioneering work of Campbell, Hess, Watson, and Banks (1978). The results of the early studies have been mixed (Birnbaum, Koslowe, & Sanet, 1977; Ciuffreda, Goldner, & Connelly, 1980; Kupfer, 1957; Mehdorn, Mattheus, Schuppe, Klein, & Kommerell, 1981; Schor & Wick, 1983; Terrell, 1981; Wick, Wingard, Cotter, & Scheiman, 1992). However, unlike most of the studies on perceptual learning in the normal population, these early training studies typically used high contrast stimuli and relatively short training periods (e.g., 7 minutes; except Kupfer, 1957) that were pre-determined irrespective of training progress and subjects' ophthalmological characteristics. ...
... The results of the early studies have been mixed (Birnbaum, Koslowe, & Sanet, 1977; Ciuffreda, Goldner, & Connelly, 1980; Kupfer, 1957; Mehdorn, Mattheus, Schuppe, Klein, & Kommerell, 1981; Schor & Wick, 1983; Terrell, 1981; Wick, Wingard, Cotter, & Scheiman, 1992). However, unlike most of the studies on perceptual learning in the normal population, these early training studies typically used high contrast stimuli and relatively short training periods (e.g., 7 minutes; except Kupfer, 1957) that were pre-determined irrespective of training progress and subjects' ophthalmological characteristics. Later studies on perceptual learning in the normal visual system showed that it typically requires several hundreds of training trials to significantly improve performance in perceptual tasks. ...
What underlies contrast sensitivity improvements in adults with anisometropic amblyopia following perceptual learning in grating contrast detection? In this paper, we adopted the external noise approach (Z.-L. Lu & B. A. Dosher, 1998) to identify the mechanisms underlying perceptual learning in adults with anisometropic amblyopia. By measuring contrast thresholds in a range of external noise conditions at two performance levels (79.3% and 70.7%), we found that a mixture of internal additive noise reduction and external noise exclusion underlay training induced contrast sensitivity improvements in adults with anisometropic amblyopia. In comparison, normal adults exhibited only small amount of external noise exclusion under the same training conditions. The results suggest that neural plasticity may be more robust in amblyopia, lending further support of perceptual learning as a potential treatment for adult amblyopia.
... It has been previously established that (1) poor fixation stability is associated with poor monocular and binocular functions in amblyopic patients 16 www.nature.com/scientificreports/ shorter for patients with better fixational abilities of the amblyopic eye in occlusion therapy [56][57][58] ; and (3) fixation stability can be improved in childhood 80 and even in adult patients over the critical period of development [81][82][83][84][85] . This is the first report, to our knowledge, showing that the more similar the fixation stability between the eyes, the more likely a patient classified as stereoblind according to Titmus test is to develop a certain level of stereopsis as a result of binocular treatment, regardless of etiology or severity of amblyopia and, more importantly, regardless of age. ...
Dichoptic therapy is a promising method for improving vision in pediatric and adult patients with amblyopia. However, a systematic understanding about changes in specific visual functions and substantial variation of effect among patients is lacking. Utilizing a novel stereoscopic augmented-reality based training program, 24 pediatric and 18 adult patients were trained for 20 h along a three-month time course with a one-month post-training follow-up for pediatric patients. Changes in stereopsis, distance and near visual acuity, and contrast sensitivity for amblyopic and fellow eyes were measured, and interocular differences were analyzed. To reveal what contributes to successful dichoptic therapy, ANCOVA models were used to analyze progress, considering clinical baseline parameters as covariates that are potential requirements for amblyopic recovery. Significant and lasting improvements have been achieved in stereoacuity, interocular near visual acuity, and interocular contrast sensitivity. Importantly, astigmatism, fixation instability, and lack of stereopsis were major limiting factors for visual acuity, stereoacuity, and contrast sensitivity recovery, respectively. The results demonstrate the feasibility of treatment-efficacy prediction in certain aspects of dichoptic amblyopia therapy. Furthermore, our findings may aid in developing personalized therapeutic protocols, capable of considering individual clinical status, to help clinicians in tailoring therapy to patient profiles for better outcome.
... However, in standardized randomized clinical trials, the effects have been smaller (Falcone et al. 2021). Much greater improvement was observed in an earlier study in which amblyopes were hospitalized to receive an intensive 6-week intervention with 100% patching of the fellow eye and various kinds of fixation training with small targets (Kupfer 1957). There are similar reports from vision therapy, although the details of the treatment vary from patient to patient (Press 1997). ...
For four decades, investigations of the biological basis of critical periods in the developing mammalian visual cortex were dominated by study of the consequences of altered early visual experience in cats and nonhuman primates. The neural deficits thus revealed also provided insight into the origin and neural basis of human amblyopia that in turn motivated additional studies of humans with abnormal early visual input. Recent human studies point to deficits arising from alterations in all visual cortical areas and even in nonvisual cortical regions. As the new human data accumulated in parallel with a near-complete shift toward the use of rodent animal models for the study of neural mechanisms, it is now essential to review the human data and the earlier animal data obtained from cats and monkeys to infer general conclusions and to optimize future choice of the most appropriate animal model.
Expected final online publication date for the Annual Review of Vision Science, Volume 8 is September 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
... Even though occlusion therapy is thought to be maximally effective if administered during the sensitive period for amblyopia (so within the first 6-8 years of age) there is some evidence showing residual plasticity of the amblyopic visual system of older children and young adults, even though a more aggressive treatment is required to obtain some improvement in young adults (Kupfer, 1957). More evidence in favour of a residual plastic potential of the adult amblyopic visual system is obtained from studies showing an improvement of the amblyopic eye acuity following a visual loss of the fellow eye (macular degeneration, El Mallah, Chakravarthy, & Hart, 2000, refractive errors, Rahi et al., 2002). ...
In this research binocular rivalry is used as a tool to investigate different aspects of visual and multisensory perception. Several experiments presented here demonstrated that touch specifically interacts with vision during binocular rivalry and that the interaction likely occurs at early stages of visual processing, probably V1 or V2. Another line of research also presented here demonstrated that human adult visual cortex retains an unexpected high degree of experience-dependent plasticity by showing that a brief period of monocular deprivation produced important perceptual consequences on the dynamics of binocular rivalry, reflecting a homeostatic plasticity. In summary, this work shows that binocular rivalry is a powerful tool to investigate different aspects of visual perception and can be used to reveal unexpected properties of early visual cortex.
... Some believe that a treatment response is unlikely after the age of six or seven years, while others consider the age of nine or ten years to be the upper age limit for successful treatment [6][7][8][9][10]. However, there are many studies involving older children and adults with amblyopia, responding to treatment with patching [11][12][13][14][15][16][17][18][19][20][21][22][23][24]. ...
... 4,5 About 25% of patients have a visual acuity in the amblyopic eye worse than 20/100, and about 75% have an acuity of 20/100 or better. 4,6-8 Although some authors have reported benefits of treating amblyopia even in adulthood, [9][10][11] it is generally held that the response to treatment seems best when instituted at an early age 12,13 and is poor after age 8 years. [14][15][16] Occlusion therapy with patching of the sound eye has been the mainstay of amblyopia treatment despite the lack of meaningful data demonstrating its superiority compared with other modalities. ...
Objective: To compare patching and atropine as treatments for moderate amblyopia in children younger than 7 years. Methods: In a randomized clinical trial, 419 children younger than 7 years with amblyopia and visual acuity in the range of 20/40 to 20/100 were assigned to receive either patching or atropine at 47 clinical sites. Main Outcome Measure: Visual acuity in the amblyopic eye and sound eye after 6 months. Results: Visual acuity in the amblyopic eye improved in both groups (improvement from baseline to 6 months was 3.16 lines in the patching group and 2.84 lines in the atropine group). Improvement was initially faster in the patching group, but after 6 months, the difference in visual acuity between treatment groups was small and clinically inconsequential (mean difference at 6 months, 0.034 logMAR units; 95% confidence interval, 0.005-0.064 logMAR units). The 6-month acuity was 20/30 or better in the amblyopic eye and/or improved from baseline by 3 or more lines in 79% of the patching group and 74% of the atropine group. Both treatments were well tolerated, although atropine had a slightly higher degree of acceptability on a parental questionnaire. More patients in the atropine group than in the patching group had reduced acuity in the sound eye at 6 months, but this did not persist with further follow-up. Conclusion: Atropine and patching produce improvement of similar magnitude, and both are appropriate modalities for the initial treatment of moderate amblyopia in children aged 3 to less than 7 years.
... However, it is now evident that visual function can improve in adults with amblyopia. The gold-standard amblyopia treatment for children consists of optical correction followed by occlusion therapy (Holmes & Clarke, 2006) and there is evidence that similar approaches can also improve visual acuity in at least a subset of older children and adults with amblyopia (Kupfer, 1957;Scheiman et al., 2005;Simmers & Gray, 1999;Wick et al., 1992). These effects seem to be particularly reliable when occlusion of the fellow eye is combined with visual perceptual learning paradigms. ...
Dichoptic training is designed to promote binocular vision in patients with amblyopia. Initial studies have found that the training effects transfer to both binocular (stereopsis) and monocular (recognition acuity) visual functions. The aim of this study was to assess whether dichoptic training effects also transfer to contrast sensitivity (CS) in adults with amblyopia. We analyzed CS data from 30 adults who had taken part in one of two previous dichoptic training studies and assessed whether the changes in CS exceeded the 95% confidence intervals for change based on test-retest data from a separate group of observers with amblyopia. CS was measured using Gabor patches (0.5, 3 and 10 cpd) before and after 10 days of dichoptic training. Training was delivered using a dichoptic video game viewed through video goggles (n = 15) or on an iPod touch equipped with a lenticular overlay screen (n = 15). In the iPod touch study, training was combined with anodal transcranial direct current stimulation of the visual cortex. We found that dichoptic training significantly improved CS across all spatial frequencies tested for both groups. These results suggest that dichoptic training modifies the sensitivity of the neural systems that underpin monocular contrast sensitivity.
Copyright © 2015. Published by Elsevier Ltd.
... Pediatrik Göz Hastalıkları Çalışma Grubu'nun bu konudaki çok merkezli çalışmasının sonuçlarının yayınlanmasına kadar bazı yazarlar, 6-7 yaştan sonra kapama tedavisinin yararlı olmadığına inanırken bazı yazarlar ise bu yaş sınırının 9-10 olduğuna inanmakta idi (1)(2)(3)(4)(5) . Altı-yedi yaş civarı genel olarak görsel gelişimin son noktası olarak kabul edildiği için bu yaştan sonraki çocuklarda yapılan kapama tedavisinin yararı uzun yıllar tartışmalara neden olmuştur ve bu konuyla ilgili çoğu retrospektif olan birçok çalışma yapılmıştır (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18) . Pediatrik Göz Hastalıkları Çalışma Grubu'nun yaptığı çok merkezli çalışmada daha önce kapama tedavisi yapılmamış çocuklarda 2-6 saat arası kapama tedavisi maksimum optik düzeltme beraber 7-12 yaş arası çocuklarda %67, 13-17 yaş arası çocuklarda ise %47 görsel başarı ile neticelenmiştir (19) . ...
AMAÇ: Yedi yaşından sonra tespit edilmiş olan ve daha önce gözlük dışında herhangi bir tedavi almamış olan anizometropik ambliyopili çocuklarda maksimum optik düzeltme ve kapama tedavisinin sonuçlarını değerlendirmek.
YÖNTEMLER: Yedi-on iki yaş arası 25 ve 13-17 yaş arası 17 anizometropik ambliyopi hastasının dosyaları geriye yönelik incelendi. Yedi-on iki yaş arası grup 1, 12-17 yaş arası grup 2 olarak kabul edildi. Tedavi süresince hastaların iki sıra ve daha fazla görme artışı sağlanması başarı olarak kabul edildi. Tedavi başarısı iki yaş grubu arasında karşılaştırıldı. Ambliyopi şiddeti, ambliyopi nedeni ve daha önce gözlük kullanımı olup olmamasının tedavi başarısına etkisi değerlendirildi.
BULGULAR: Tedavi başarısı grup 1’de %76, grup 2’de %41 olarak tespit edildi. Özellikle grup 2’de ambliyopi şiddeti ağır olanlarda tedavi başarısı daha yüksekti ama iki grupta da bu açıdan anlamlılık tespit edilmedi. İki grupta da hipermetrop olanlardaki başarı astigmat olanlara göre daha yüksekti. Daha önce gözlük kullanmamış olanlarda başarı oranı daha yüksekti.
SONUÇ: Daha önce kapama tedavisi yapılmamış 7-17 yaş arası anizometropik ambliyopi hastalarında maksimum optik düzeltme ile beraber kapama tedavisi yapılması görsel başarı sağlamaktadır.
... [6][7][8][9][10] However, there are many studies involving older children and adults with amblyopia, responding to treatment with patching. [11][12][13][14][15][16][17][18][19][20][21][22][23][24] Occlusion therapy with patching of the sound eye has been the conventional treatment. However, there are many studies stating the effectiveness of some pharmacological agents in the treatment of amblyopia -citicoline is one of them. ...
Aim:
To study the effectiveness of the addition of citicoline to patching in the treatment of amblyopia in the age group of 4-13 years.
Materials and methods:
A randomized controlled trial, which included patients who were randomly divided into two groups. Both the groups received patching therapy till plateau was achieved in phase 1 of the study. Then in phase 2, group I received citicoline plus patching and group II continued to receive only patching.
Outcome measures:
Outcome was measured by the visual acuity in logMAR every month in phase 1 till plateau was achieved and then for 12 months in phase 2.
Results:
No significant difference was found in the mean visual acuities in these two groups in phase 1 till plateau was reached. In phase 2, for the initial four months, there was no significant difference in the visual acuities in these two groups, at the respective intervals. However, five months onward, up to 12 months, there was a significant difference in the visual acuities in these groups.The result was the same in younger patients (< seven years of age) as well as in older patients (> seven years of age). In phase 2, the mean proportional improvement in group I was significantly more than that in group II, at two months and onward, at the respective intervals.
Conclusion:
The improvement in visual acuity with citicoline plus patching was significantly more than that with patching alone, in one year of treatment.
... Active eye exercises, such as exercises requiring fixation, tracking, and eye-hand coordination, with feedback, combined with patching of the nonamblyopic eye, have been successful in inducing visual improvements in adult amblyopes. In a pioneering study, Kupfer (1957) hospitalized six strabismic amblyopes with acuity of 20/200 or worse in the amblyopic eye. During the 4-week intervention, the good eye was patched full-time and the patient spent many hours doing fixation exercises with the amblyopic eye that were designed to promote steady foveal fixation. ...
In this introductory article, we summarize the evidence from humans and animal models on the shaping of postnatal visual development by focused binocular input. When balanced input is missing during a sensitive period, deficits emerge, including seemingly permanent impairments in visual acuity that are labeled amblyopia. Rodent models have identified neurochemical changes that control the onset of such sensitive periods and molecular and structural brakes that lead to the diminution of the plasticity thereafter. Both animal and human studies of amblyopia have recently identified exciting ways to remediate vision in adulthood that bear some similarity to the interventions that have proved successful in promoting recovery from stroke.
... For amblyopes, once they have passed the sensitive period for spatial vision (usually before 6-8 years of age), the visual system is fully (though erroneously) developed and therefore no longer subject to therapeutic modifications. On the other hand, several studies reported marked visual acuity improvements in adult amblyopes (Birnbaum, Koslowe, & Sanet, 1977;Kupfer, 1957;Polat et al., 2004;Simmers & Gray, 1999;Wick, Wingard, Cotter, & Scheiman, 1992). In addition, a large number of recent studies have demonstrated remarkable plasticity in the adult visual system (Chino, 1995;Dragoi, Sharma, & Sur, 2000;Levine, 1988;Pizzorusso, Medini, Berardi, Chierzi, & Fawcett, 2002;Safran & Landis, 1996). ...
To evaluate the effects of perceptual learning on contrast-sensitivity function and visual acuity in adult observers with amblyopia, 23 anisometropic amblyopes with a mean age of 19.3 years were recruited and divided into three groups. Subjects in Group I were trained in grating detection in the amblyopic eye near pre-training cut-off spatial frequency. Group II received a training regimen of repeated contrast-sensitivity function measurements in the amblyopic eye. Group III received no training. We found that training substantially improved visual acuity and contrast-sensitivity functions in the amblyopic eyes of all the observers in Groups I and II, although no significant performance improvement was observed in Group III. For observers in Group I, performance improvements in the amblyopic eyes were broadly tuned in spatial frequency and generalized to the fellow eyes. The latter result was not found in Group II. In a few cases tested, improvements in visual acuity following training showed about 90% retention for at least 1 year. We concluded that the visual system of adult amblyopes might still retain substantial plasticity. Perceptual learning shows potential as a clinical tool for treating child and adult amblyopia.
... Fahle & Poggio, 2002;Gilbert, 1996;Gilbert, Sigman, & Crist, 2001;Goldstone, 1998;Ramachandran, Cobb, & Yang, 1994), deprivation (Fine, Smallman, Doyle, & MacLeod, 2002;He, Hodos, & Quinlan, 2006; Komatsu, 2006;Mendola, Conner, Sharma, Bahekar, & Lemieux, 2006) and even abnormal development, as in amblyopia (e.g. Kupfer, 1957;Levi & Polat, 1996;Levi, Polat, & Hu, 1997;Polat, MaNaim, Belkin, & Sagi, 2004;Simmers & Gray, 1999;Zhou et al., 2006). The present review will, following a brief description of visual plasticity in the normal, adult brain, attempt to summarize the state of the field related to perceptual plasticity after damage to the adult visual system. ...
Plasticity appears to be a ubiquitous property of nervous systems, regardless of developmental stage or complexity. In the visual system of higher mammals, perceptual plasticity has been intensively studied, both during development and in adulthood. However, the last few years have seen some significant controversies arise about the existence and properties of visual plasticity after permanent damage to the adult visual system. The study of perceptual plasticity in damaged, adult visual systems is of interest for several reasons. First, it is an important means of unmasking the relative contribution of individual visual areas to visual learning, adaptation and priming, among other plastic phenomena. Second, it can provide knowledge that is essential for the development of effective therapies to rehabilitate the increasing number of people who suffer the functional consequences of damage at different levels of their visual hierarchy. This review summarizes the available evidence on the subject and proposes that visual plasticity may be just as ubiquitous after damage as it is in the intact visual system. However, damage may alter visual plasticity in ways that are still being defined.
This fourth edition of Clinical Management of Binocular Vision uses the past five years of research studies and literature to provide an accurate look at today's diagnosis and treatment of binocular vision. Written with an emphasis on proper evaluation, diagnosis, and treatment, each condition is covered in-depth and includes background information, symptoms, case analysis, and management options. This edition also includes the latest information on new vision therapy equipment. Easy to read and understand, this book is ideal for faculty when designing courses, students studying these topics for the first time, or established practitioners looking for a practical, easy-to-use reference on accommodative, ocular motility, and nonstrabismic vision anomalies. Features: • Material presented by diagnostic category for easy reference • Case studies presented at the end of each chapter to demonstrate how information pertains to real life • Uses the latest research and evidence to support the evaluation and treatment protocols suggested • Over 200 illustrations - now in full color!.
New behavioral treatment methods, including dichoptic training, perceptual learning, and video gaming, have been proposed to improve visual function in adult amblyopia. Here, we conducted a meta-analysis of these methods to investigate the factors involved in amblyopia recovery and their clinical significance.
Mean and individual participant data meta-analyses were performed on 24 studies using the new behavioral methods in adults. Studies were identified using PubMed, Google Scholar, and published reviews.
The new methods yielded a mean improvement in visual acuity of 0.17 logMAR with 32% participants achieving gains ≥ 0.2 logMAR, and a mean improvement in stereo sensitivity of 0.01 arcsec-1 with 42% of participants improving ≥2 octaves. The most significant predictor of treatment outcome was visual acuity at the onset of treatment. Participants with more severe amblyopia improved more on visual acuity and less on stereo sensitivity than those with milder amblyopia. Better initial stereo sensitivity was a predictor of greater gains in stereo sensitivity following treatment. Treatment type, amblyopia type, age, and training duration did not have any significant influence on visual and stereo acuity outcomes.
Our analyses showed that some participants may benefit from the new treatments; however, clinical trials are required to confirm these findings. Despite the diverse nature of the new behavioral methods, the lack of significant differences in visual and stereo sensitivity outcomes among them suggests that visual attention-a common element among the varied treatment methods-may play an important role in amblyopia recovery.
Training studies using action video games have shown enhanced post-training vision in both normally-sighted as well as amblyopic individuals. The purpose of this work has been the development of a game modification or “mod” using Unreal Tournament 2004 in order to combine conventional antisuppression therapy principles for amblyopia with the benefits rendered by action video games for visual recovery and binocularity in amblyopia. The game system involves a stereo display with a degraded image shown to the "good" eye and game event items shown only to the amblyopic eye. Reward and punishment in the game is partially based on attendance with the amblyopic eye. Current results from a trial with 4 subjects show that all subjects recovered visual acuity and reported a dramatic reduction in switching between eyes with training, and were able to use their eyes simultaneously. A large sample clinical study is currently underway to further assess game efficacy.
To ascertain whether conventional treatment can improve visual function in adults with amblyopia.
Sixteen patients aged 21-67 years old were instructed to wear glasses for refractive correction and to patch the non-amblyopic eye for at least 1 h per day. Visual acuity, measured with crowded optotypes for distance and near acuity, was checked every 3 months, and followed for a mean (SD) of 14.1 (4.2) months. Prognostic factors related to the subsequent results, an improvement of 3 or more lines logMAR in distance visual acuity, were evaluated.
Of 16 patients, 5 (31 %) improved 3 or more lines of distance and 5 (31 %) in near acuity. The mean improvement in distance was 2.4 lines logMAR (95 % CI 1.4-3.5) and 2.4 lines logMAR for near acuity (95 % CI 1.5-3.3). Patients aged under 45 years (p = 0.0357) and with severe amblyopia (p = 0.0337), defined as a corrected distance visual acuity of worse than -0.699 logMAR, were associated with a good response.
Conventional treatment may improve the visual acuity of amblyopic eyes even in adult patients.
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Amblyopia is a visual impairment secondary to abnormal visual experience (e.g., strabismus, anisometropia, form deprivation) during early childhood that cannot be corrected immediately by glasses alone. It is the most common cause of monocular blindness globally. Patching remains the mainstay of treatment, but it is not always successful and there are also compliance and recurrence issues. Because amblyopia is a neural disorder that results from abnormal stimulation of the brain during the critical periods of visual development, it is essential to understand the neural mechanisms of amblyopia in order to devise better treatment strategies. In this review, I examine our current understanding of the neural mechanisms that underlie the characteristic deficits associated with amblyopia. I then examine modern neuroimaging findings that show how amblyopia affects various brain regions and how it disrupts the interactions among these brain regions. Following this, I review current concepts of brain plasticity and their implications for novel therapeutic strategies, including perceptual learning and binocular therapy, that may be beneficial for both children and adults with amblyopia.
The treatment of the infant who is born with sensory deprivation amblyopia is one of the most difficult therapeutic problem sets facing the ophthalmologist today. This group of anomalies has many forms, the most common of which seems to be unilateral and bilateral cataracts. Substantial advances have been made, however, in many aspects of therapy for infants who have this set of problems.
We have come to realize that it is essential to address these conditions at the first moment that is consistent with the safety of the child. New techniques in cataract extraction have reduced the time course of surgical treatment, reduced the frequency of secondary cataracts, and sustained the patency of the visual pathway.
Unfortunately, practitioners who engage in the surgery may not have the back-up skills in advanced contact lens fitting, correction of aniseikonia, and, in some instances, the strabismological complications which are encountered. Further, improved means of assessment of visual acuity, binocular vision, and other visual characteristics of these infants are only in the developmental stages at this time.
Thus, we propose to present the problem in an orderly manner. We shall first review the types of cases and problems. We will then discuss surgical techniques and the information which must be determined during examination under anesthesia (EUA) for the purposes of visual correction. We will then describe the designs of the spectacle lens and/or spectacle/contact lens combinations that are used to correct the resultant aniseikonia and anisometropia. We will address the approaches to patching and techniques on how to best achieve binocular vision in these patients.
Separately, means and methods of assessment of vision by preferential looking, visual evoked response, optokinetic nystagmus, and tests of other visual functions will be explored. In summary, we will try to tie together the entire therapeutic regimen that can be used in the treatment of these patients.
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:1).What factors influence the outcome of perceptual learning?2).Specificity and generalization – two sides of the coin.3).Do the improvements last?4).How does PL improve visual function?5).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.
Neural plasticity plays a crucial role in human development. During development, neural networks are shaped by experience-dependent processes that selectively strengthen and prune connections so that those that remain match the environment and process it optimally. Over time, neural connections become more stable, forming widely distributed, interconnected networks involving balanced excitation and inhibition and structural stabilizers like myelin. It was long believed that the potential for organization or reorganization existed only during early development. However, the successful treatments for adults with stroke or amblyopia discussed in this issue suggest that the potential for significant reorganization persists well into adulthood. Thus, development can be thought of as the stabilization of connections to match the current environment but with considerable residual plasticity that can be revealed if there is a shift in the excitatory: inhibitory balance or the removal of the structural stabilizers.
There are striking similarities between the visual defect of amblyopia and the motor deficit of the extremities produced by such types of damage to the central nervous system (CNS) as stroke and traumatic brain injury, both after and before maturity. Part of the motor deficit of the extremities following CNS injury can be attributed to a learning phenomenon termed "learned nonuse" or if present from birth, "developmental disregard." The same mechanism is hypothesized to be involved in the development of amblyopia. Treatments that are efficacious in the remediation of these defects, Constraint-Induced Movement therapy and amblyopia training, also share a number of strong similarities. In addition, plastic brain changes are produced by CI therapy and are hypothesized to occur during amblyopia training.
To evaluate changes in corrected distance visual acuity (CDVA) after photorefractive keratectomy (PRK) in amblyopic cases.
Ankara Ataturk Training and Research Hospital 1st Ophthalmology Clinic, Ankara, Turkey.
Retrospective case series.
The medical records of cases of anisometropic amblyopia treated by excimer laser PRK were reviewed. Inclusion criteria were no previous refractive correction, occlusion treatment, or chemical penalization before age 15 years. Anisometropic amblyopia was defined as a more than 2-line difference in CDVA and a refractive error difference greater than 3.00 diopters (D) between 2 eyes of the same patient. Final visual acuity measurements were performed at the end of the sixth postoperative month.
The study enrolled 16 hyperopic patients and 34 myopic patients with a mean age of 33.3 years. The mean preoperative spherical equivalent was -7.46 D ± 2.90 (SD) in myopic eyes and +4.15 ± 2.56 D in hyperopic eyes. The differences between the preoperative and postoperative uncorrected distance visual acuity and CDVA were statistically significant (P=.001). The mean CDVA was 0.47 ± 0.17 preoperatively and 0.61 ± 0.19 postoperatively. The CDVA decreased in 3 cases (6%), stayed the same in 12 cases (24%), and increased in 35 cases (70%). There was no statistically significant correlation between the severity of amblyopia and the increase in CDVA (r = 0.20, P=.165).
After PRK to eliminate and correct refractive errors in anisometropic amblyopia, visual acuity improved significantly in 70% of adult patients with no previous occlusion or chemical penalization treatment.
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 (more than 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 programs, there is no alternative therapy available later in life. More recently, burgeoning evidence has begun to reveal previously unrecognized levels of residual neural plasticity in the adult brain and scientists have developed new genetic, pharmacological, and behavioral 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.
PURPOSE. To evaluate the use of liquid crystal glasses (LCG) for the treatment of amblyopia caused by refractive errors, strabismus, or both. METHODS. In this noncomparative, prospective, interventional case series, 28 children (age range, 4-7.8 years) with monocular amblyopia participated, of which 24 completed the study. In the LCG, the occluding and nonoccluding phases of the flicker were electronically set in all patients at a fixed rate. The rate was set so that accumulated occlusion was 5 hours during 8 hours' weartime. Occlusion was applied only to the good eye. All 24 children were followed up regularly for 9 months. Best corrected VA for distance and near, fixation patterns, and binocular function were measured. VA for distance was measured with the Snellen chart and for near with the Rossano/Weiss chart. RESULTS. Mean VA for distance at the end of the study (after 9 months) was 0.59 (SD, 0.16) compared with 0.27 (SD, 0.09) at the beginning (P < 0.001). Most of the children (92%) complied well with the treatment. (Good compliance was defined as wearing the LCG for at least 8 hours per day.) Stereopsis at the end of treatment was good (better than 60 sec arc) in 21% of the children compared with 8% at the beginning. No serious adverse events were recorded. CONCLUSIONS. The use of LCG in patients with amblyopia yielded an improvement in near and distance VA and in stereopsis. Treatment was well accepted by children and parents.
Experience-dependent plasticity is closely linked with the development of sensory function; however, there is also growing evidence for plasticity in the adult visual system. This review re-examines the notion of a sensitive period for the treatment of amblyopia in the light of recent experimental and clinical evidence for neural plasticity. One recently proposed method for improving the effectiveness and efficiency of treatment that has received considerable attention is 'perceptual learning'. Specifically, both children and adults with amblyopia can improve their perceptual performance through extensive practice on a challenging visual task. The results suggest that perceptual learning may be effective in improving a range of visual performance and, importantly, the improvements may transfer to visual acuity. Recent studies have sought to explore the limits and time course of perceptual learning as an adjunct to occlusion and to investigate the neural mechanisms underlying the visual improvement. These findings, along with the results of new clinical trials, suggest that it might be time to reconsider our notions about neural plasticity in amblyopia.
Orthoptic therapy was instituted in an 11-year-old patient having deep amblyopia, constant small-angle esotropia with anomalous retinal correspondence, and a past history of minimal success with such therapy. This combination of factors pointed toward a poor prognosis for substantial recovery of vision function. Rate of recovery of several monocular and binocular vision functions was monitored during the course of 18 months of intensive orthoptic therapy. Results showed marked improvement in several monocular vision functions, suggesting presence of considerable residual neural plasticity of multiple sites in the visual pathways of this older amblyope.
Orthoptic therapy was instituted in an adult, alternating esotrope with asthenopia who exhibited inaccurate static accommodative responses with adequate, clinically determined, accommodative facility. During and following therapy the patient showed considerable improvement in accommodative accuracy and related visual functions, such as contrast sensitivity, in the absence of any change in strabismic deviation. This case provides the first laboratory documentation of orthoptic effects on accommodation in an adult strabismic.
Amblyopia is a neuronal abnormality of vision that is often considered irreversible in adults. We found strong and significant improvement of Vernier acuity in human adults with naturally occurring amblyopia following practice. Learning was strongest at the trained orientation and did not transfer to an untrained task (detection), but it did transfer partially to the untrained eye (primarily at the trained orientation). We conclude that this perceptual learning reflects alterations in early neural processes that are localized beyond the site of convergence of the two eyes. Our results suggest a significant degree of plasticity in the visual system of adults with amblyopia.
Amblyopia has a 1.6-3.6% prevalence, higher in the medically underserved. It is more complex than simply visual acuity loss and the better eye has sub-clinical deficits. Functional limitations appear more extensive and loss of vision in the better eye of amblyopes more prevalent than previously thought. Amblyopia screening and treatment are efficacious, but cost-effectiveness concerns remain. Refractive correction alone may successfully treat anisometropic amblyopia and it, minimal occlusion, and/or catecholamine treatment can provide initial vision improvement that may improve compliance with subsequent long-duration treatment. Atropine penalization appears as effective as occlusion for moderate amblyopia, with limited-day penalization as effective as full-time. Cytidin-5'-diphosphocholine may hold promise as a medical treatment. Interpretation of much of the amblyopia literature is made difficult by: inaccurate visual acuity measurement at initial visit, lack of adequate refractive correction prior to and during treatment, and lack of long-term follow-up results. Successful treatment can be achieved in at most 63-83% of patients. Treatment outcome is a function of initial visual acuity and type of amblyopia, and a reciprocal product of treatment efficacy, duration, and compliance. Age at treatment onset is not predictive of outcome in many studies but detection under versus over 2-3 years of age may be. Multiple screenings prior to that age, and prompt treatment, reduce prevalence. Would a single early cycloplegic photoscreening be as, or more, successful at detection or prediction than the multiple screenings, and more cost-effective? Penalization and occlusion have minimal incidence of reverse amblyopia and/or side-effects, no significant influence on emmetropization, and no consistent effect on sign or size of post-treatment changes in strabismic deviation. There may be a physiologic basis for better age-indifferent outcome than tapped by current treatment methodologies. Infant refractive correction substantially reduces accommodative esotropia and amblyopia incidence without interference with emmetropization. Compensatory prism, alone or post-operatively, and/or minus lens treatment, and/or wide-field fusional amplitude training, may reduce risk of early onset esotropia. Multivariate screening using continuous-scale measurements may be more effective than traditional single-test dichotomous pass/fail measures. Pigmentation may be one parameter because Caucasians are at higher risk for esotropia than non-whites.
Critical periods for experience-dependent plasticity are ubiquitous. The idea that experience-dependent plasticity is closely linked with the development of sensory function is still widely held; however, there also is growing evidence for plasticity in the adult nervous system. This article reviews the notion of a critical period for the treatment of amblyopia in light of recent experimental and clinical evidence for neural plasticity. Specifically, adults with amblyopia can improve their perceptual performance via extensive practice on a challenging visual task, and this improvement may transfer to improved visual acuity. Amblyopes achieve this improvement via the mechanisms that have been shown to explain perceptual learning in the normal visual system. It is hypothesized that these same mechanisms account for at least some of the improvement that occurs in the treatment of amblyopia.
Amblyopia, a major cause of vision loss, is a developmental disorder of visual perception commonly associated with strabismus (squint). Although defined by a reduction in visual acuity, severe distortions of perceived visual location are common in strabismic amblyopia. These distortions can help us understand the cortical coding of visual location and its development in normal vision, as well as in amblyopia. The history of retinotopic mapping in the visual cortex highlights the potential impact of amblyopia. Theories of amblyopia include topological disarray of receptors in primary visual cortex, undersampling from the amblyopic eye compared with normal eyes, and the presence of anomalous retinal correspondence or multiple cortical representations of the strabismic fovea. We examined the distortions in a strabismic amblyope, using a pop-out localization task, in which normal observers made errors dependent on the visual context of the stimulus. The localization errors of the strabismic amblyope were abnormal. We found that none of the available theories could fully explain this one patient's localization performance. Instead, the observed behavior suggests that multiple adaptations of the underlying cortical topology are possible simultaneously in different parts of the visual field.
To evaluate the effectiveness of treatment of amblyopia in children aged 7 to 17 years.
At 49 clinical sites, 507 patients with amblyopic eye visual acuity ranging from 20/40 to 20/400 were provided with optimal optical correction and then randomized to a treatment group (2-6 hours per day of prescribed patching combined with near visual activities for all patients plus atropine sulfate for children aged 7 to 12 years) or an optical correction group (optical correction alone). Patients whose amblyopic eye acuity improved 10 or more letters (> or =2 lines) by 24 weeks were considered responders.
In the 7- to 12-year-olds (n = 404), 53% of the treatment group were responders compared with 25% of the optical correction group (P<.001). In the 13- to 17-year-olds (n = 103), the responder rates were 25% and 23%, respectively, overall (adjusted P = .22) but 47% and 20%, respectively, among patients not previously treated with patching and/or atropine for amblyopia (adjusted P = .03). Most patients, including responders, were left with a residual visual acuity deficit.
Amblyopia improves with optical correction alone in about one fourth of patients aged 7 to 17 years, although most patients who are initially treated with optical correction alone will require additional treatment for amblyopia. For patients aged 7 to 12 years, prescribing 2 to 6 hours per day of patching with near visual activities and atropine can improve visual acuity even if the amblyopia has been previously treated. For patients 13 to 17 years, prescribing patching 2 to 6 hours per day with near visual activities may improve visual acuity when amblyopia has not been previously treated but appears to be of little benefit if amblyopia was previously treated with patching. We do not yet know whether visual acuity improvement will be sustained once treatment is discontinued; therefore, conclusions regarding the long-term benefit of treatment and the development of treatment recommendations for amblyopia in children 7 years and older await the results of a follow-up study we are conducting on the patients who responded to treatment.
Contrast sensitivity improves in visually normal children until 7 years of age and is impaired in children who experienced early visual deprivation from bilateral congenital cataracts. Here, we investigated whether the deficits after early visual deprivation change during childhood by retesting the contrast sensitivity of seven patients treated for bilateral congenital cataract who had been first tested before 7.5 years of age, and of two patients first tested after 11 years of age. For the younger group, contrast sensitivity at low spatial frequencies improved after 1- and 2-year intervals, while their sensitivity at mid and high spatial frequencies did not change. There was no systematic change in the two older patients. The results indicate that early visual input sets up the neural substrate for later improvement in contrast sensitivity at mid and high spatial frequencies. However, there is sufficient plasticity during middle childhood to allow some recovery at low spatial frequencies. The results shed new light on the role of early visual experience and the nature of developmental plasticity.
Within the last five years, there have been a number of exciting new advances in our knowledge and understanding of amblyopia. This article reviews recent psychophysical studies of naturally occurring amblyopia in humans. These studies suggest that: 1) There are significant differences in the patterns of visual loss among the clinically defined categories of amblyopes. A key factor in determining the nature of the loss is the presence or absence of binocularity. 2) Dysfunction within the amblyopic visual system first occurs in area V1, and the effects of amblyopia may be amplified downstream. 3) There appears to be substantial neural plasticity in the amblyopic brain beyond the "critical period."
One way to assess the influence of retinal image motion on visual functioning in congenital nystagmus (CN) is to examine the effects of comparable image motion in observers with normal vision. A second approach is to evaluate visual functioning in subjects with CN when the retinal image motion is reduced. Using these approaches, we determined that spatial contrast sensitivity and visual acuity are not limited by the parameters of retinal image motion in some subjects with CN, but rather by a form of amblyopia. Clinical evidence from patients with bilateral refractive amblyopia suggests that a gradual improvement of visual acuity may be possible in persons with CN, if the optimal refractive correction is worn and parameters of the retinal image motion undergo long-term amelioration.
Infantile nystagmus (IN) has been reported to decrease with convergence. However, previous studies reported equivocal results regarding a corresponding improvement in acuity with near viewing. The aim of this study was to determine whether visual acuity improves with near viewing in patients with IN.
In the first experiment, visual acuities were measured using clinical test charts at standard test distances of 3 or 6 m and 40 cm and using S Charts at 3.75 m and 40 cm. In the second experiment, visual acuities were measured using a Bailey-Lovie chart at distance and a Lighthouse modified ETDRS near card held by each subject at his or her preferred working distance. S-chart acuities were obtained again at 3.75 m and 40 cm for comparison. Horizontal eye movements were recorded using infrared limbal reflection for 20 of the 34 subjects in the first experiment and for all 20 subjects in the second experiment.
The S-chart acuities measured at distance and near were almost all within 0.1 logMAR (logarithm of the minimum angle of resolution) in experiments 1 and 2. Clinically measured acuity averaged nearly one line better at 40 cm than at distance in experiment 1, but the mean difference between near acuity using the ETDRS card and distance acuity using the Bailey-Lovie chart was less than one letter in experiment 2. No consistent relationship existed between the changes in visual acuity with viewing distance and the subject's eye movements.
Despite a reduction of nystagmus at near distances in many patients with IN, the visual acuity at near does not improve significantly. These results imply that visual acuity in patients with IN is determined primarily by sensory limitations rather than by the moment-by-moment characteristics of these patients' eye movements.
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