You are on page 1of 7

b i o m e d i c a l j o u r n a l 3 8 ( 2 0 1 5 ) 5 1 0 e5 1 6

Available online at www.sciencedirect.com

ScienceDirect
Biomedical Journal
journal homepage: www.elsevier.com/locate/bj

Review Article

The challenges of amblyopia treatment
Gail D.E. Maconachie, Irene Gottlob*
Ulverscroft Eye Unit, Department of Neuroscience, Psychology and Behaviour,
University of Leicester, RKSCB, Leicester Royal Infirmary, Leicester LE2 7LX, UK

article info

abstract

Article history:

The treatment of amblyopia, particularly anisometropic (difference in refractive correction)

Received 9 April 2014

and/or strabismic (turn of one eye) amblyopia has long been a challenge for many clini-

Accepted 8 June 2015

cians. Achieving optimum outcomes, where the amblyopic eye reaches a visual acuity

Available online 28 February 2016

similar to the fellow eye, is often impossible in many patients. Part of this challenge has
resulted from a previous lack of scientific evidence for amblyopia treatment that was

Keywords:

highlight by a systematic review by Snowdon et al. in 1998. Since this review, a number of

Amblyopia

publications have revealed new findings in the treatment of amblyopia. This includes the

Treatment

finding that less intensive occlusion treatments can be successful in treating amblyopia. A

Occlusion

relationship between adherence to treatment and visual acuity has also been established

Review

and has been shown to be influenced by the use of intervention material. In addition, there
is growing evidence of that a period of glasses wearing only can significantly improve visual acuity alone without any other modes of treatment. This review article reports findings since the Snowdon's report.

Unilateral amblyopia is a loss in visual function in one eye in
comparison to the other and is often caused by other associated factors that force the visual system to prefer one eye over
another [1]. The most common of these factors is a difference
in refractive error between the two eyes, usually in spherical
correction (anisometropic amblyopia) and/or a strabismus
(strabismic amblyopia). Many other forms of unilateral
amblyopia occur as a result of pathological changes in the
structure in or around the eye such as unilateral cataracts or
ptosis (stimulus deprivation amblyopia). A challenge in the

treatment of amblyopia is that there is often no apparent
structural reason why there is a limitation of vision and yet
many amblyopes, after several years of amblyopia treatment,
fail to reach successful outcomes.
Since as early as the 1st century AD [2] covering of the
dominant eye to increase visual acuity in the amblyopic eye,
now referred to as occlusion therapy, has been suggested as
the standard form of treatment in anisometropic and strabismus amblyopia. However, it was not until the Snowdon's
report [3] in 1998 that it became apparent that evidence-based

* Corresponding author. Ophthalmology Group, University of Leicester, RKSCB, Leicester Royal Infirmary, Leicester LE2 7LX, UK.
Tel.: þ44 (0) 116 258 6291; fax: þ44 (0) 116 255 8810.
E-mail address: Ig15@le.ac.uk (I. Gottlob).
Peer review under responsibility of Chang Gung University.
http://dx.doi.org/10.1016/j.bj.2015.06.001
2319-4170/Copyright © 2016, Chang Gung University. Publishing services provided by Elsevier B.V. This is an open access article under
the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

In a study by Atkinson et al. Moseley et al. Limitations of this study include no randomized control group and the inclusion of patients with an intraocular difference of 0. Further work in this area with a larger cohort is needed to explore the relationships between glasses wearing. This generated a wide variance between departments on how amblyopic patients were treated clinically [14]. were similar to the lower amount of prescription 2 h and 6 h respectively. This highlights the need for further research into refractive treatment for example a RCT comparing refractive adaptation and other treatment modalities for amblyopia. a number of additional studies have confirmed that this period of refractive treatment does occur in anisometropic and/or strabismic amblyopes [10e12].1) had a resolution of their amblyopia with glasses alone. Refractive therapy In children with amblyopia. In 1998.18 LogMAR with the majority of cases achieving maximum improvement within the first 18 weeks of wearing refractive correction. there is some confliction within literature with regards prescribing full prescription due to its possible effects on emmetropization. it has been reported that the recommended 18e22 weeks may. An unpublished pilot study including 26 patients [13]. Therefore. [7] reported the results of 13 anisometropic and strabsimic amblyopes who were prescribed refractive correction only. Until occlusion therapy was prescribed based on clinical experience rather than scientific based evidence. There is also a wide variance in the length of time required to achieve the maximum outcome of refractive 511 adaptation [12]. for some patients. Further investigation regarding the amount of hyperopia that affects emmetropization is still required. When refractive adaptation is translated into a clinical setting. strabismic or strabismus with anisometropia) p ¼ 0. moderate and severe strabismic and anisometropic amblyopes into two groups with the moderate amblyopes receiving either 6 h or 2 h of occlusion.85). However.b i o m e d i c a l j o u r n a l 3 8 ( 2 0 1 5 ) 5 1 0 e5 1 6 research about treatment modalities in amblyopia was lacking.29. Although at present there is still a wide variance in the number of hours of occlusion prescribed by those treating amblyopia. One of the possible factors is the influence of adherence to glasses wear.0001). has revealed variable adherence to glasses wear. refractive adaption and visual outcome. the effect on emmetropization was significantly delayed in comparison to those who were poor compliers or were not prescribed any refractive correction.76. The mean improvement in visual acuity for the 65 patients was 0. It has also shown a strong doseeresponse relationship between adherence and visual outcome (r ¼ 0.17]. recommend that patients should be reassessed at 6 and 14 weeks and if there is no significant improvement they suggest prescribing other forms of treatment. As a result of these findings. However. This review will explore the new findings since this report and discuss future areas of interest for amblyopia treatment. This period of refractive correction is also commonly referred to as refractive adaptation or refractive treatment [8]. it is recommended that full refractive correction should be prescribed [4]. Their results revealed that visual outcomes with more intensive occlusion. delay treatment. 6 h for moderate amblyopes and full time for severe amblyopes. There was no significant difference in the level of improvement between different types of amblyopia. Guidelines from the American Academy of Ophthalmologist [18] and the Royal College of Ophthalmologist [19] have changed as a result of these findings so that now both advise the use of 6 h for severe amblyopia and 2 h for moderates. In a later study [8]. Occlusion How much? The use of occlusion therapy is the most well-known and commonly practiced way of treating amblyopia. 14 of 65 amblyopic subjects (interocular difference in visual acuity of >0. whereas the severe amblyopes received either full time (all or all but 1 h 4/day) or 6 h of occlusion [16. Adherence to occlusion There is some concern with basing guidelines on the PEDIG studies because adherence to occlusion therapy is less than optimal. the PEDIG [15] sought to review the number of hours prescribed by recruiting. the results shown by the PEDIG group have been challenged by the work objectively exploring compliance in amblyopia treatment with the use of occlusion dose monitors (ODMs) [20. they showed for the first time that amblyopic subjects can gain significant improvements in visual outcome with refractive correction alone.1 which is not often described as amblyopia. (anisometropic. It has been also reported to have a greater effect in those with better baseline stereopsis. The least likely type of amblyopia to respond to refractive adaption has been reported to occur in strabismus with anisometropia amblyopia. [5] they found that those who were prescribed a partial correction in comparison to those who were prescribed no refractive correction the process of emmetropization was the same. [10]. Norris et al. there has been a significant increase in publications of randomized controlled studies in amblyopia. p ¼ 0. it was shown that patients who were prescribed 6 h or 3 h a day only adhered to half of their prescribed amount. milder forms of anisometropic amblyopia and those with a worse baseline visual acuity in strabismus with anisometropia and strabismic patients. showed that those who were prescribed full correction from the age of 6 months and had good adherence to glasses wear. In addition. leading to there being no significant difference in the total amount of occlusion therapy undertaken . In one study. and no further treatment was required.21]. a recent survey of orthoptists reported 94% prescribe a period of refractive correction before implementing further treatment. although this is lower for strabismic (75%) or strabismic and anisometropic amblyopia (79%) [9]. In contrast. In 2002. (n ¼ 287) [6]. average 2 h 33 min and 1 h 45 min respectively. a randomized control trial (RCT) study by Ingram et al. Since this study. in particular when a strabismus is present. their findings revealed no significant difference between cause of amblyopia and improvement in visual acuity (p ¼ 0.

Recently. establishing routine. It is suggested however that in comparison to occlusion.2 or even 0. which is lower than the usually defined difference of 0. Type of amblyopia. the same authors reported that occlusion with near task was insignificant [28]. there was no significant difference between the number of patients in which amblyopia recurred.1. two groups of patients.50) [21]. An additional inverse relationship has also been found between recurrence and age [31]. in the only reported RCT of 20 patients who underwent full-time occlusion. difficulties with distress in the child who was patching and relationship pressures particularly in the early stages of treatment. A number of key themes were highlighted including parents being unsure about the benefits of treatment. Studies have also begun exploring reasons for poor adherence to occlusion therapy in order to produce better compliance. Many recommended the use of rewards. Initial research suggests that moderate patching treatment (6e8 h of occlusion) should undergo a period of weaning [32]. the intervention material significantly reduced the number of drop-outs and reduced the number of poorly compliant patients. Tjiam et al. Atropine With the increasing knowledge of poor compliance during patching and the potential cause of social deprivation as result of occlusion therapy [36]. with and without weaning treatment [34]. Another group reported subjects who underwent 3 h or 6 h occlusion therapy with near tasks and again showed undertaking near tasks while patching significantly improved visual outcomes [29]. The result showed that cartoons produce a significant improvement in compliance in comparison to a control group. semi-opaque foils that can be attached to the glasses. but there was a suggestion that children who had not yet undergone treatment could also improve. Parents were also asked for suggestions that could help compliance.45) h/day of occlusion although this was not significantly different to the amount necessary for <4 years. Recurrence A challenge of amblyopia treatment is recurrence of amblyopia on cessation of treatment. it has been suggested that patients should undergo a period of maintenance or weaned occlusion. A number of factors have been associated with this recurrence including better vision at the end of treatment. However. greater improvement during treatment. had a significant improvement in visual outcome in comparison to a control group who were only prescribed glasses. In a pilot RCT study published by the PEDIG group [27]. The role of atropine is to blur the vision in the nonamblyopic eye by paralyzing the ciliary muscles that control accommodation and constriction of the pupil. reward calendars and parent information leaflets. which included 64 children. Additional studies have explored ways of improving visual outcomes through increasing the stimulation of the amblyopic eye during occlusion.512 b i o m e d i c a l j o u r n a l 3 8 ( 2 0 1 5 ) 5 1 0 e5 1 6 between the two groups [21]. Dixon-Wood et al. Bangerter foils do provide less distress for the patient and therefore could be considered as a possible alternative.45e6. Although this treatment has been recommended since .19 respectively) but again this was not significant. patients with strabismic amblyopia required more hours of occlusion therapy than anisometropic amblyopes (5.3 as used in the PEDIG studies. [26]. in unpublished work where participants did not have prolonged refractive adaptation. showed that 2 h of occlusion with advised near tasks did suggest an increase in visual outcome in comparison to those who were not advised to undertake near activities while patching.79 and 5.55 (4. The findings however were not significant for >12 years. greater numbers are needed to compare to the larger PEDIG study. Partial occlusion therapy has also been suggested to help with compliance in the form of Bangerter foils. a significant dose response relationship was found up to 10 h for strabismic and strabismus with anisometropia amblyopes but not in anisometropes [22]. [23] interviewed 25 parents of children who underwent occlusion therapy in order to find reasons for reduced compliance. p ¼ 0. From this advice. [25] reported using several intervention materials in low-socioeconomic groups. there was no significant difference in visual outcome for any cause of amblyopia [30]. Older children (older than 6 years) required a higher average of 5. However. including cartoons. Further evidence is required to explore the possibility of differing treatment based on the type of amblyopia. with various types of amblyopia. decoration of the patch or educational cartoons [24]. suggested to be around the age of 8 years of age. Later with a larger number of amblyopes (n ¼ 425) and longer follow-up (up to 17 weeks). A large multicenter study by PEDIG in 2005 [35] revealed that 50% of children aged between 7 and 12 years of age who underwent a period of amblyopia treatment. many research groups have initiated the development of intervention material. This finding has been supported by another study [11]. dose response relationship plateaued around 4 h particularly in children <4 years [11].00013. were prescribe 10 h/day of occlusion therapy and were reviewed 12 weeks later. In a clinical setting. such as occlusion or atropine. Critical period Recent reports have challenged the clinical perception that amblyopes cannot be treated beyond the critical period. In 2006. It is reported that 13e24% of patients decrease by 2 or more LogMAR lines within the 1st year of completing treatment [31e34]. either anisometropic and/or strabismic was found not to be a predictor of visual outcome. atropine is often used in clinic as an alternative to occlusion.1. r ¼ 0. history of recurrence and a combination of strabismus with and without anisometropia or microtropia. where refractive adaptation was prescribed prior to occlusion. however. a control group and a intervention group. a small angled strabismus with abnormal binocular functions. A larger RCT is required to re-affirm this finding. However. aged 3 to <7 years. In another study by Pradeep et al. A limitation of this study was the inclusion of patients with a difference in visual acuity between the eyes of 0. Dose response relationships between hours of effective patching measured by ODMs and visual outcome revealed a strong correlation up to 6 h in a study including 52 participants (F ¼ 17. in a RCT comparing Bangerter foils to glasses alone or occlusion. in a study with more participants (n ¼ 97). Although the overall compliance between the two groups was similar. Similarly.

Large multicenter RCT have revealed a number of previously unknown benefits including the use of atropine being instilled only at the weekends producing similar visual outcomes to weekday instillation and the finding that severe amblyopes can also be treated effectively [37]. an image is presented to both eyes.51]. particularly in patients beyond the critical period. usually Tetris. which increases levodopa uptake into the bloodebrain barrier [57]. however. The treatment of severe amblyopia with atropine still requires further investigation as at present this is limited to an RCT comparing the effects of 2 h of occlusion therapy and atropine in children 7e12 years. 513 An adaption of perceptual learning is to use stimulation to both eyes to treat amblyopia [51]. Subgroup analysis of type of amblyopia has no effect on long-term visual outcomes (p ¼ 0. is surprising as it has been reported that atropine can only blur visual acuity to a maximum of 20/100 in the nonamblyopic eye [38]. there were no previous RCTs. Both studies show a decline in visual outcomes after 8e10 weeks although less significant in the binocular group [49. Initial results report a significant improvement in visual outcome in the amblyopic eye [48e50]. With the availability and improvements of computers. Even though atropine is reported to be better tolerated and a less emotional experience than occlusion therapy [43]. . in the form of a placebo-control trial is warranted. have been reported in a number of studies [55. the image in the dominant eye is slowly increased until the contrast in both eyes is equal. A greater amount of research has been undertaken investigating the treatment of moderate amblyopes with atropine in comparison to occlusion. Pilot data show promising results with improvements in visual outcome and stereopsis in the majority of patients. very few studies report the size of the strabismic deviation except Li et al. During perceptual learning. including visual acuity. the size of strabismic deviations in strabismic subjects was also not reported. patients are often trained on contrast sensitivity tasks while nonamblyopic eye is occluded [46. usually as a result of poor compliance [9]. More recent game play formats have also been used to increase stimulation of the amblyopic eye [48. The final point. Recent discoveries in mice have shown that the lynx1 gene codes for a protein that suppresses acetylcholine receptor signaling in the brain and regulates plasticity of the mature brain [61]. again similar to occlusion therapy. Side effects from levodopa are commonly reported in literature and limit its use in a clinical setting however further work. This game requires the use of both eyes by presenting only half the blocks to each eye. However. Moreover. In addition.b i o m e d i c a l j o u r n a l 3 8 ( 2 0 1 5 ) 5 1 0 e5 1 6 before the Snowdon's report. although not significant. atropine is still commonly only used as a secondary option after occlusion has been unsuccessful. In all studies except one. especially if adherence to occlusion is optimized with the use of intervention. Despite the equivalent outcomes between occlusion and atropine. improvement in vision in comparison to the atropine group [40e42]. the dominant eye is presented with a low contrast eye while the amblyopic eye is given a high contrast eye. Patients are trained using a dichoptic game format. due to low study number. due to the current sample size in both studies. In 1990. perceptual learning has begun to regain increasing interest. Comparisons between occlusion and atropine at long-term outcomes are reported to have a similar visual outcome in moderate amblyopes. If subjects are successful in completing the game.56] and are enhanced by the use of occlusion therapy and carbidopa. no analysis was undertaken to explore the effects of the cause of amblyopia on visual outcome. Improvements in other visual functions. Regression of VA outcomes after ceasing levodopa are high although more sustained in those who receive fulltime occlusion and are younger (3e7 years) [58e60]. no analysis based on type of amblyopia was performed. During treatment. Pharmacological treatment Levodopa is the most commonly reported medical drug used in amblyopia treatment and is a precursor to dopamine. RCTs with long term follow-up. Acupuncture The use of acupuncture for the treatment of medical conditions has long been discussed in the literature but has only relatively recently been applied to amblyopia treatment. sub-analysis of amblyopia cause has not yet been undertaken. Cholinesterase inhibitors may prevent the expression of lynx1 allowing for plasticity in the brain beyond the critical period that would be beneficial in amblyopia treatment and has already begun to form the basis of future research. Gottlob and StanglerZuschrott [54] first described the use of levodopa in severe strabismic and strabismic with anisometropia amblyopia and reported a significant improvement in suppression scotomas and contrast sensitivity outcomes when treated with levodopa. Two studies have followed-up subjects after monocular and binocular treatment. The limitation of many perceptual learning studies is the lack of large scale. Due to the sample sizes. Occlusion therapy (minimum 6 h a day to maximum 10 h a day) was revealed to have a quicker initial. This does not accurately reflect the amount of occlusion suggested for severe amblyopia particularly in this older age group [39]. The use of CAM significantly decreased when little benefit in comparison to occlusion therapy was found [45]. Perceptual learning The idea of perceptual learning was first defined by Eleanor Gibson (1963) and involved training patients on perceptual tasks with the Cambridge Visual Stimulator (CAM) a system that used high contrast rotating sine-wave gratings [44]. it is not clear whether occlusion therapy could achieve better visual outcomes than atropine. with the use of animal model [53]. The stereopsis outcomes have also been reported to be enhanced using transcranial direct current stimulation [52]. suggested by the PEDIG group.49]. to be reduced in amblyopia. Moreover. all forms of amblyopia were recruited into the study.47]. [50] who recruited 3/10 strabismic subjects of a deviation greater than 10 prism dioptres. Further analysis with greater number of subjects would help to establish suitable subtypes of amblyopia that would benefit from this form of treatment.83). Dopamine is a neurotransmitter present within the visual pathway which has been shown.

[3] Snowdon S. Effectiveness of preschool vision screening. Using a randomized cross-over trial method. lasting long-term effects and no control group.12:44e5. Stewart-Brown S. Other treatments Several other suggestions have been reported as an alternative to the conventional treatment for amblyopia. The initial study reported the results of two groups of anisometropic amblyopes aged 7e12 years. To prescribe or not to prescribe? Guidelines for spectacle prescribing in infants and children. have strabismus. St. further research is still required to help those treating amblyopia particularly in regards to improvement and maintaining compliance to treatment. Additional research could also help to provide more reliable treatment options. At 15 weeks. Louis. McNamara R. Lambert TW. Many have developed in order to address the issue with poor compliance to either glasses or occlusion therapy [65e67]. while revealing that refractive adaptation. Compliance issues remain a Source of support The Ulverscroft Foundation. although studies have positively addressed this by increasing the amount of information provided to families. and did not. McCarry B. amblyopia research has advanced significantly particularly with the use of randomized controlled trials.and videorefractive screening. [7] Moseley MJ.27 lines and 1. Braddick O. [5] Atkinson J. Neufeld M. references [1] von Noorden GK. Saudi Arabia: Obiekan Publishing House. Conflict of interest None declared.83 lines respectively) [63].84:324e6. we now have reliable scientific evidence to show that prescribing refractive correction and atropine or occlusion with additional interventional material should optimize visual outcomes in amblyopic patients with minimal side effects. King J. An additional difficulty is compliance with maintenance issues particularly with contact lenses where good hygiene practice is required [67]. Nurs Stand 1997. Br J Ophthalmol 2000. however. An additional limitation in the first study was that the acupuncture group required more clinical visits than the occlusion group leading to a possible Hawthorne effect (positive attention bias). Rice T. In conclusion. Ehrlich D. Gill LE. Currently. [2] Qurrah TI. occlusion and penalization can improve visual acuity in amblyopia this has led to the raising of additional questions that require further investigation. to improve blood flow in the visual cortex through accurate stimulation using the correct acupoints [62]. These limitations would need to be further addressed before implementation into clinical practice particularly in areas where acupuncture is not a common treatment in any medical condition. Conclusion Since the Snowdon's report. Effect of spectacles on changes of spherical hypermetropia in infants who did. Vision and perception. 2002. More recently. With the increasing knowledge of the role occlusion and glasses plays individually in the improvement of the amblyopic eye. RCTs are required to investigate these relationships. With high-risk of reversal amblyopia. important that these treatment methods undergo robust clinical trials so that further clarification of the types of amblyopia that will benefit with gameplay treatments can be established. The first group received acupuncture while the second group (control groups) received 2 h of occlusion therapy. 1991. Charnock A. 4th ed. Although both studies revealed a benefit of acupuncture a significant limitation was absence of a control group to assess for placebo effect. However.10(Pt 2):189e98. Eye (Lond) 1996. Riyadh. since the Snowdon's report. using fMRI. et al. follow-up subjects in the acupuncture group were found to have significantly greater improvements in visual acuity in comparison to the control group (2.94:514e27. Further. MO: Mosby. Although refractive surgery has proven successful in adults. [4] Leat SJ. Clin Exp Optom 2011. Binocular vision and ocular motility: theory and management of strabismus. it is difficult to warrant their merit in comparison to occlusion. two RCT using acupuncture in amblyopia treatment have been reported. treating amblyopes with game-play could potentially initiate a new form of amblyopia treatment.69]. Two infant vision screening programmes: prediction and prevention of strabismus and amblyopia from photo. It is. significant problem. The main concern is the increased risk that many of these suggested treatments have in comparison to occlusion therapy. Other more controversial nonrandomized prospective trials have reported the use of sutured occluders or silicone lid closures to promote the use of the weaker eye [68. Anker S. [6] Ingram RM. although advancements have been made. research should continue to find more specific treatment protocols for the various types of amblyopia. Lam et al. However. et al. they found significantly greater improvements in visual acuity in the phases that corresponded with the use of acupuncture. With the growing public interest in binocularity and computer systems. Robier B. [64] reported the effects of acupuncture on anisometropic children aged 3e7-year-old who were undergoing refractive adaption. Research in the area of refractive correction compliance. Very few have been translated into clinical practice although significant improvements have been noted in refractive surgery and occlusive contact lenses treatment.514 b i o m e d i c a l j o u r n a l 3 8 ( 2 0 1 5 ) 5 1 0 e5 1 6 Acupuncture has been shown. it is not clear what longterm effects it has on young children particularly when the eye is still continuing to develop. RCTs between binocular treatments and occlusion therapy are also still warranted. Remediation of refractive . binocular treatment and more education on atropine is also needed.

Stephens DA. Farooq S. A randomized trial of patching regimens for treatment of moderate amblyopia in children. Differences in the management of amblyopia between European countries. Alotaibi AG. Iran Red Crescent Med J 2011. Predictors and a remedy for noncompliance with amblyopia therapy in children measured with the occlusion dose monitor. Stephens DA.rcophth. Cotter SA. Kraker RT. Fielder AR.335:707. Collier J. Modeling dose-response in amblyopia: toward a child-specific treatment plan. Beck RW.126:1039e44. Hertle RW. et al. Saudi Med J 2012. Walsh LA.org/ppp [accessed 24. Royal College of Ophthalmologists. Beck RW. Arch Ophthalmol 2003.119:150e8. Gottlob I. et al. Moseley MJ.98:865e70. Wallace DK. Felius J.03. et al. Amblyopia. Newsham D. A randomized trial of near versus distance activities while patching for amblyopia in children aged 3 to less than 7 years. Edwards AR. 2006. Proudlock FA. Ophthalmology 2003. Norris JH. Sharma P. Kraker RT. Dixon-Woods M. North RV. Everett DF. Fielder AR. Maconachie G. Kutschke P. Ophthalmic Physiol Opt 2002. 998e1004. Quinn GE. Shailesh G. Pediatric Eye Disease Investigator Group Writing Committee. Beck RW. Alenazy BR. San Francisco. Graefes Arch Clin Exp Ophthalmol 2007. Arnold RW.121:603e11. Repka MX. Kraker RT. Scott WE. Beck RW. Birch EE. et al. Risk of amblyopia recurrence after cessation of treatment.117. Looman CW.86. Pfeifer W. Holmes JM. Johnson DA.03. Birch EE. Kraker RT. Tacagni DJ. Thompson JR.12:493e7. Ophthalmology 2006. Beck RW. Cotter SA. Invest Ophthalmol Vis Sci 2006. Holmes JM. Klimek DL. Cole SR. Stewart CE. Br J Ophthalmol 2003. et al. Holmes JM. Birch EE. Graefes Arch Clin Exp Ophthalmol 2013. Hahn EK. et al. Fielder AR. .91:491e4. Birch EE. Fawazi SM. Abu-Amero KK. Fielder AR.48:2589e94. Awan M. Arch Ophthalmol 2003. et al. Holmes JM. The method of treatment cessation and recurrence rate of amblyopia.126:1634e42. Simonsz-To Vermeulen-Jong MH. Repka MX. Birch EE. Holmes JM. Recurrence of amblyopia after occlusion therapy.13:258e63. Stewart CE.33:395e8. Medghalchi AR. van der Maas PJ. Arch Dis Child 2006. A randomized trial of prescribed patching regimens for treatment of severe amblyopia in children. CA: American Academy of Ophthalmology.9:129e36.17:107e16. Arch Ophthalmol 2005. Bush G. Pediatric Eye Disease Investigator Group. ROTAS Cooperative. A randomized pilot study of near activities versus non-near activities during patching therapy for amblyopia.113:2097e100. Hertle RW.121:1625e32. Birch E. Proudlock FA. Beck RW. Holmes JM. Beck RW. Gottlob I. et al. Why is compliance with occlusion therapy for amblyopia so hard? A qualitative study.251:321e9. Invest Ophthalmol Vis Sci 2005. Kraker RT. Holtslag G. Ophthalmology 2012. Moseley MJ. A randomized trial of atropine vs patching for treatment of moderate amblyopia. Cotter SA. BMJ 2007.15]. LaRoche GR.47:4393e400. Moseley MJ. Borsboom GJ.87:291e6. Cotter SA. Birch E. Effect of compliance to glasses wear on the outcome of visual acuity after refractive adaptation. Gottlob I. A randomized trial of atropine vs patching for treatment of moderate amblyopia: follow-up at age 10 years. A randomized controlled trial of unilateral strabismic and mixed amblyopia using occlusion dose monitors to record compliance.88:1552e6. Scheiman MM. J AAPOS 2008. Ophthalmic Physiol Opt 1991. Hook J. Outcomes of 3 hours part-time occlusion treatment combined with near activities among children with unilateral amblyopia.245:811e6. Holmes JM. Saxena R. et al. Cole SR. Kelly ME. Scheiman MM. Randomised comparison of three tools for improving compliance with occlusion therapy: an educational cartoon story. Awan M. Invest Ophthalmol Vis Sci 2012.115:2071e8.  th B. Ophthalmology 2008. Gottlob I. 2012. Van Minderhout HM. Awan M. et al. Repka MX. et al. An audit of the Royal College of Ophthalmologists strabismic amblyopia treatment protocol: a departmental review. Beck RW.110:2075e87. Tjiam AM. Invest Ophthalmol Vis Sci 2007. Stewart CE. Tan JH. Preferred practice pattern® guidelines. American Academy of Ophthalmology Pediatric Ophthalmology/Strabismus Panel. Fronius M. Awan M. Strabismus 2009. Foster NC.15]. Astle WF.2:255e6. Available from: http://www. Lazar EL.8:420e8. Br J Ophthalmol 2014. Strabismus 2009. Edwards AR. Chandler DL.b i o m e d i c a l j o u r n a l 3 8 ( 2 0 1 5 ) 5 1 0 e5 1 6 [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] amblyopia by optical correction alone. Beck RW. J AAPOS 2005. MOTAS Cooperative. Bonsall DJ. Holmes JM. The effect of recent amblyopia research on current practice in the UK.pdf [accessed 24. a reward [26] [27] [28] [29] [30] [31] [32] [33] [34] [35] [36] [37] [38] [39] [40] [41] [42] 515 calendar. Simonsz B.53:5609. Guidelines for the management of amblyopia. Pradeep A.ac. Pradeep A. Cotter SA. Ophthalmology 2010. J AAPOS 2009. Pilling RF.94:1352e7.aao.13:578e81. Can amblyopia treatment be optimised? Acta Ophthalmol 2008. Br J Ophthalmol 2010. Moseley MJ. Pediatric Eye Disease Investigator Group. Treatment of severe amblyopia with weekend atropine: results from 2 randomized clinical trials. Kraker RT. Cotter SA. Beck RW. Arch Ophthalmol 2008. Clinical trial of patching versus atropine penalization for the treatment of anisometropic amblyopia in older children. Patching vs atropine to treat amblyopia in children aged 7 to 12 years: A randomized trial. Awan M. An educational intervention to improve adherence to high-dosage patching regimen for amblyopia: a randomised controlled trial. Gottlob I. A randomized trial comparing Bangerter filters and patching for the treatment of moderate amblyopia in children. Bush G. Impact of patching and atropine treatment on the child and family in the amblyopia treatment study. et al. Bhola R. Atropine occlusion in the treatment of strabismic amblyopia and its effect upon the non-amblyopic eye. et al. Melia BM. Rutstein RP.e6. Proudlock FA. Objectively monitored patching regimens for treatment of amblyopia: randomised trial.17:78e81. The pediatric eye disease investigator group. Beck RW. J AAPOS 1998. Repka MX.uk/docs/publications/Guidelines fortheManagementofAmblyopia. Keech RV. Br J Ophthalmol 2004.123:437e47. Avaliable from: http://www. and an information leaflet for parents.46:1435e9. Loudon SE. J AAPOS 2004. Menon V.11:113e7. Paediatric Subcommittee of the Royal College of Ophthalmologists.22:296e9. Randomized trial of treatment of amblyopia in children aged 7 to 17 years. Gottlob I. Dalili S. MOTAS Cooperative. Stewart CE. Arch Ophthalmol 2008. Stephens DA. Optical treatment of strabismic and combined strabismic-anisometropic amblyopia. Writing Committee for the Pediatric Eye Disease Investigator Group. Refractive adaptation in amblyopia: quantification of effect and implications for practice. Factors affecting the stability of visual function following cessation of occlusion therapy for amblyopia.

et al.29:396e400. Bremer DL. Arch Ophthalmol 2010.23:R308e9. et al. Video-game play induces plasticity in the visual system of adults with amblyopia. J Refract Surg 2013. Invest Ophthalmol Vis Sci 1981. [57] Leguire LE. [51] Li J. Bremer DL. [64] Lam DS. [65] Althomali TA. Functional magnetic resonance imaging detects activation of the visual association cortex during laser acupuncture of the foot in humans. [55] Gottlob I. J Pediatr Ophthalmol Strabismus 2010. limits plasticity in adult visual cortex. Stewart H. Sutured protective occluder for severe amblyopia. Shansky MS. Lam DS. Kaufman LM.52:7195e204. Dutton GN. Science 2010. Arch Ophthalmol 2008. Klein SA. Koch DD. Clarke J. Purdy J. Cole SR. Rogers GL. Ophthalmology 2011. Nguyen J. Chen LJ. Posterior chamber toric phakic IOL implantation for the management of pediatric anisometropic amblyopia. [48] Cleary M. McMahon TT. [49] Li RW. Buchanan A. Hill M. et al. Malmheden A. Beck RW. Effect of levodopa on contrast sensitivity and scotomas in human amblyopia. Lynx1. McGregor ML. Prolonged perceptual learning of positional acuity in adult amblyopia: perceptual template retuning dynamics.2:257e64. Levi DM. Interactive binocular treatment (I-BiT) for amblyopia: results of a pilot study of 3D shutter glasses system. Limstrom SA. [61] Morishita H. Miwa JM. Chandler DL. Holmes JM. Yu M.14:389e95. McGraw PV. Bremer DL. et al. Schlager A. Visual acuities and scotomas after one week levodopa administration in human amblyopia. Bacal DA. Cobb S. Coats DK. Arch Ophthalmol 2010. Ophthalmology 2006. Deng D. a cholinergic brake. Sharma A. Hussein MA. Walson P. Hadjiconstantinou-Neff M. [56] Leguire LE.27:1077e83. Levodopa and childhood amblyopia. Chan LY. Pilot study of levodopa dose as treatment for residual amblyopia in children aged 8 years to younger than 18 years. Long-term outcomes of photorefractive keratectomy for anisometropic amblyopia in children. [54] Gottlob I. Lin Q.64:339e41.126:891e5. Ruff CC. Experience with the CAM vision stimulator: preliminary report. Armitage MD. [50] Herbison N. Randomized controlled trial of patching vs acupuncture for anisometropic amblyopia in children aged 7 to 12 years. Development of receptive field properties of retinal ganglion cells in kittens raised with a convergent squint. Zhao J. Wang Y. Gaber El-Hag Y. Curr Biol 2013. Deng D. [52] Spiegel DP. [62] Siedentopf CM. Neurotherapeutics 2013. Hensch TK.38:62e7.47:157e62. J Pediatr Ophthalmol Strabismus 2001. Charlier J. Dean L. Chen LJ. [63] Zhao J.79:376e80.39:313e20. Kraker RT. Samir A. Ash I. [46] Li RW.327:53e6.33:2722e8. Visual acuities after levodopa administration in amblyopia. Gregson R. [66] Paysse EA.118:1501e11. Wang Y. Moody AD. Br J Ophthalmol 1980.516 b i o m e d i c a l j o u r n a l 3 8 ( 2 0 1 5 ) 5 1 0 e5 1 6 [43] Felius J. Invest Ophthalmol Vis Sci 1990. Vats P. Byblow WD. Mottaghy FM. [59] Repka MX. Occlusion and levodopa-carbidopa treatment for childhood amblyopia. [47] Astle AT.9:e1001135. The effectiveness of occluder contact lenses in improving occlusion compliance in patients that have failed traditional occlusion therapy.29:290e8. Transcranial direct current stimulation enhances recovery of stereopsis in adults with amblyopia. [44] Willshaw HE. Yu M. Zheng C. J AAPOS 1998. Golaszewski SM. Eye (Lond) 2009. Eye (Lond) 2013. Eastgate R. [68] Hakim OM. Invest Ophthalmol Vis Sci 2011. et al.28:14223e9. . Williams A. Silicone-eyelid closure to improve vision in deeply amblyopic eyes. Levi DM. Felber S. et al. Chu RH.20:400e6. Malik KP. The pattern of learned visual improvements in adult amblyopia. J AAPOS 2010. Neurosci Lett 2002.128:1510e7. Li J. Optom Vis Sci 2002. J Pediatr Ophthalmol Strabismus 1992.31:776e80. [58] Mohan K. [60] Dadeya S. Dhankar V. [53] Chino YM. Evaluation of the CAM treatment for amblyopia: a controlled study. [67] Joslin CE. Adjunctive effect of acupuncture to refractive correction on anisometropic amblyopia: one-year results of a randomized crossover trial. Atkinson CS. PLoS Biol 2011.113:169e76. Hamill MB. Stangler-Zuschrott E. Hess RF. Rogers GL. Exp Brain Res 1980.330:1238e40. J Neurosci 2008. Walson PD. Zheng C. Lin Q. J Pediatr Ophthalmol Strabismus 2009. Levodopa/carbidopa in the treatment of amblyopia. Thompson B. Labow-Daily LS. Heintz N. Hamasaki DI. [69] Arnold RW. Hess RF. Reinecke RD. Assessment of a computer-based treatment for older amblyopes: the Glasgow Pilot Study. Dichoptic training enables the adult amblyopic brain to learn. Webb BS. Ngo C.10:831e9. Evaluating the burden of amblyopia treatment from the parent and child's perspective.23:124e31. Invest Ophthalmol Vis Sci 1992.128:1215e7. [45] Tytla ME.46:87e90.