Clinical and Experimental Vision and Eye Research

Show Contents

Binocular treatment of amblyopia
  CLEVER
REVIEW ARTICLE
Binocular treatment of amblyopia
Savleen Kaur1, Subhash Dadeya2
1Department of Ophthalmology, Advanced Eye Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India
2 Department of Ophthalmology, Guru Nanak Eye Centre, Maulana Azad Medical College, New Delhi, India
Address for correspondence: Dr. Subhash Dadeya, Department ofOphthalmology, Guru Nanak Eye Centre,Maulana Azad Medical College, New Delhi,India 110001.
Ph: 91-9968604336.
Email: dadeyassi@gmail.com
Received 14 July 2018;
Accepted 24 July 2018
doi: 10.15713/ins.clever.9
 
ABSTRACT
Amblyopia is the most common cause of monocular vision loss in children andpopulation under 40 years, with an estimated prevalence of 1-5%. Amblyopia is causedby a prolonged period of abnormal retinal stimulation due to strabismus (ocularmisalignment), anisometropia (refractive imbalance), or both (combined) and leadsto functional deficits including reduced contrast sensitivity, poor spatial localization,poor stereovision, and foveal crowding. The present treatments for amblyopia arepredominately monocular, aiming to improve the vision in the amblyopic eye. Recentevidence shows that amblyopes possess binocular cortical mechanisms for boththreshold and suprathreshold stimuli. Hence, there is an ongoing search for binocularstimulation methods. Detecting the condition early increases the chances of successfultreatment and the earlier it is detected, more successful will be the treatment in equalizingvision in both eyes. If it is not treated timely, it can cause permanent loss of vision. Thisarticle reviews the recent advances in amblyopia management and how they can be putto clinical practice.
Keywords: Amblyopia, lazy eye, penalization, patchingtherapy
How to cite this article: Kaur S, Dadeya S. BinocularTreatment of Amblyopia. Cli Exp Vis Eye Res J 2018;1(1):44-47.
 
 

Introduction

Amblyopia is one of the most challenging subspecialtiesencountered in pediatric ophthalmology. Amblyopia is themost common cause of monocular vision loss in children andpopulation under 40 years, with an estimated prevalence of1-5%. Amblyopia is caused by a prolonged period of abnormalretinal stimulation due to strabismus (ocular misalignment),anisometropia (refractive imbalance), or both (combined) andleads to functional deficits including reduced contrast sensitivity,poor spatial localization, poor stereovision, and foveal crowding.The pathophysiology of amblyopia is being advanced withthe development of newer imaging modalities and increasedunderstanding of the cortical pathways. Newer horizons arebeing explored in amblyopia management. The recent researchhas focused on the binocular treatment of amblyopia in contrastto the conventional uniocular patching.

Conventionally, the amblyopia treatment consists of ageappropriatespectacle prescription followed by occlusion oratropine penalization of the better fellow eye. The equivalentefficacy of patching versus atropine penalization was established bythe earlier amblyopia treatment studies conducted as randomizedcontrolled trials by the pediatric eye disease investigator group(PEDIG).[1-5] This article reviews the recent advances in amblyopiamanagement and how they can be put to clinical practice.

 
Need for newer modalities

Occlusion therapy is not free from side effects. Disadvantagescan be occlusion amblyopia, functional debilitation, cosmeticblemish, allergic skin rash, recurrence, poor compliance,psychological problems, ocular deviation due to disruption offusion, and visual decline. Penalization also suffers from potentialside effects due to systemic absorption of drug, allergic reactions,and the fact that active inhibition is not eliminated.

A study of moderate and severe amblyopia treatment foundapproximately 25% of patients under age seven had a recurrenceof amblyopia within the 1st year of stopping treatment, andchildren ages 7-12 had a 7% chance of recurrence (worsening oftwo lines of visual acuity).[6,7] This recurrence is more commonin patients with severe amblyopia who went from 6 h of patchingper day to no patching. In addition, patients with a history ofsuccessfully treated amblyopia need continued close monitoringfor a recurrence of amblyopia. 54% of children treated at age< 3-7 years still demonstrate some amblyopia at age 10 afteradequate therapy.[3] In older children, the effect is even less andaround 74% of children aged 7-12 years treated with patching,and 80% treated with atropine have some degree of residualamblyopia on long-term follow-up.[4] In children aged more than17 years, outcomes are even less effective with only one-quarter-one-half of children responding to combined treatment ofspectacles and patching depending on whether they had previoustreatment or were treatment naive (respectively).[5] Overall,among 73-90% of amblyopic children, 15-50% fail to achievenormal visual acuity after months or years of treatment.[1-5]

44 Clinical and Experimental Vision and Eye Research, January-June, Vol 1, 2018

Binocular treatment of amblyopia Kaur and Dadeya

To help prevent recurrence, patients should be weaned offpatching therapy. Residual amblyopia is another treatmentchallenge, considering vision does not improve sufficiently withone treatment for some patients.

Besides the fact that these treatment modalities havedominated the pediatric ophthalmologist world for ages, patientcompliance is poor because of the many negative side effectsof patching and drops. Furthermore, patching can cause manypsychosocial problems when trying to force a child to complywith wearing their eye patch. Kids do not want to wear their eyepatch because it impacts their quality of life and atropine dropscan cause light sensitivity and disorientation. Even the patientwho has done occlusion therapy with good compliance mayimprove visual acuity in 50-85% of cases, leading to suppression,stereo blindness, and a deficient depth perception in the rest.

Goal of newer treatment strategies
  • Perceptual learning (PL)
  • Visual processing development
  • Oculomotor therapy
  • Eye-hand coordination training.

Newer Strategies

The exact mechanism of patching therapy is still unclear;however, possible mechanisms include a reduction of interocularsuppression or a purely monocular improvement in theprocessing of signals from the amblyopic eye. Since there is sucha poor binocular outcome from patching, it can be concluded thatthe effects of patching primarily involve monocular mechanisms.Recent studies have shown that amblyopia is a binocularproblem caused by active suppression that converts a structurallyintact binocular system into a functionally monocular system.One promising approach for the treatment with amblyopia isthe combination of patching and perceptual learning (PL) inits many varied forms, for which both monocular and binocularbenefits have been documented. It has been shown that lossof binocularity is one of the defining features of amblyopia;therefore, the focus of research in this area has shifted frommonocular interventions that involve patching of the fellow eyeto approaches that directly target binocular visual function andas the primary therapeutic step. This has led to increased interestin the development of amblyopia treatments that directlyaddress binocular dysfunction by promoting binocular visionand reducing inhibitory interactions within the visual cortex.Evidence suggests that focusing on binocular treatments foramblyopia may prove to be beneficial in both improving visionand possibly improving binocularity. There are many popularsoftware's that are developed nowadays promoting binocularvision therapy with three-dimensional (3D) gaming and at thesame time stimulating binocular interaction. Some of theseare purely monocular, some are monocular under otherwisebinocular conditions, and one is purely binocular, involvingdichoptic stimulation and a dichoptic manipulation of contrastto enable simultaneous use of both eyes. These are believed totreat amblyopia not only in children but also in adults.

 
The first attempt to provide the combination of short-termocclusion (20 min), controlled visual stimulation, and attentivegameplay (noughts and crosses) was the complementary andalternative medicine (CAM) treatment. Its beneficial effectswere later isolated to the short-term nature of the occlusionand the attentive gameplay. A number of hybrid-binocularapproaches have been suggested, which are all directed torecovering monocular function under binocular viewing. Theaim is to involve the fixing eye in recovery of vision throughintensive training/detection of targets presented exclusively tothe amblyopic eye.

These treatments are based on these principles:
  • Monocular PL,
  • Monocular videogame play (VGP) and dichoptic PL/VGP.

PL

"PL" approach involves administering a single visual perceptto both eyes simultaneously or under monocular viewingconditions. A number of visual tasks have been explored as ameans to apply PL, including Vernier acuity, Gabor detection,positional discrimination, letter identification in noise, positiondiscrimination in noise, and contrast detection.[8] Various studieshave reported the beneficial effect of exercises based on PL inadult as well as juvenile amblyopes.[9-14] These positive effectshave also been noted to be more on crowding.[15] However,this improvement might be task dependent; based on the typeof activity or exercise used. It might be difficult to generalizeits benefits in all types of amblyopia. There is no doubt that PLcombined with short-term patching is much better than longertermpatching with passive stimulation in terms of improvingmonocular acuity;[14] however, its usefulness for reestablishingbinocular vision and stereopsis is less clear. PL tasks have beendone only in laboratory settings and yet have not been extrapolatedto home-based settings. These studies have been conducted insmall group of patients only in experimental setups. The utility ofthis principle in a larger number of patients, in a home setting withlonger follow-up as randomized studies, is lacking.

Clinical and Experimental Vision and Eye Research, January-June, Vol 1, 2018 45

Kaur and Dadeya Binocular treatment of amblyopia

Dichoptic training

A dichoptic treatment presents an independent stimulus to eacheye in contrast to PL, and the brain is forced to integrate theimages into a single perception. In these treatment modalities,under binocular conditions, the task given is such that it requiresbinocular integration under monocular viewing conditions. Thesignal strength coming into the patient's good eye is reducedenough so that it cannot suppress the amblyopic eye. The stimulito the amblyopic eye may be of higher contrast than the fellowgood eye. The result is binocular perception in a patient withotherwise deep suppression of the amblyopic eye. Over time, theviewing conditions are changed, and the image seen by the goodeye is suppressed less until both eyes see approximately the sameimage. These tasks have proven to be beneficial both in betweenand outside the critical period.[16-19] In the first study of its kindby Hess et al.,[17] the investigators found that at-home use of theiPod-based game for 10-30 h restored simultaneous binocularperception in 13 of 14 cases along with significant improvementsin acuity (0.11 ± 0.08 logMAR) and stereopsis (0.6 ± 0.5 logunits). Furthermore, the anaglyph and lenticular platforms wereequally effective. In addition, the iPod devices were able to recorda complete and accurate picture of treatment compliance. Onthis basis, they concluded that the home-based dichoptic iPodmobile game approach represents a viable treatment for adultswith amblyopia. Other software's based on dichoptic learningalso have been found to improve stereoacuity.

The technology was also translated into clinical practice onan iPod-based game which had the disadvantage of requiringa head position[19] and later into red-green dichoptic imagesmaking it more generalizable.[20]

Binocular iPad therapies

The principle of dichoptic training was converted to an iPadgame and put into a trial by Birch et al.[20] The hypothesis wasbased on the physiological evidence that weak, noisy signalsfrom the amblyopic eye can contribute to binocular vision ifsuppression by the fellow eye is reduced by signal attenuation, forexample, reducing stimulus contrast. There were four binoculariPad games played using red-green anaglyphic glasses. Childrenhad to move and rotate falling blocks to fit them together withbase blocks in the falling blocks game. For all four games,amblyopic eye contrast was set to 100% and, initially, fellow eyecontrast was set to 15-20%, based on the child being able to playthe games successfully during training. They demonstrated asignificant improvement in children aged 4-12 years by 4 h ofgaming therapy. However, the biggest disadvantage of the studywas that patching was not prohibited in the study.

Later on, it was put into a trial in younger children also.[21]PEDIG conducted a randomized control trial comparing 7 days/week and 1 h/day of falling blocks game versus 2 h patching andfound them equivalent. However, in the falling blocks game,studies showed a poorer compliance as the children did notfeel compelled to play the game for 1 h also.[22-24] In conclusion,the binocular iPad therapy although showed overwhelmingresults did not prove efficient to be put into clinical practice.A newer study replaced the falling blocks game with the DigRush game and demonstrated greater amblyopic eye visualacuity improvement than patching (0.15 LogMAR vs. 0.07LogMAR).[25]

 
These games achieve their therapeutic effect by presenting adifferent image to each eye, thus rewarding the patient when botheyes work together to win the game. For instance, in the stereoblock game, some of the blocks seen by the amblyopic eye are inhigh contrast, while other blocks in lower contrast are seen by thehealthy eye. The contrast level in these games can be modifiedbased on each patient's burden of disease. Furthermore, thesemobile games are easily available in every smartphone whichgives colorful binocular visual stimulus in an entertaining way,which children enjoying without any limitation.

Programmable electronic glasses

The lenses are liquid crystal display; they can also be programmedto turn opaque, occluding vision in the left or right eye fordifferent time intervals, acting like a digital patch that flickers onand off. AmblyzTM occlusion glasses were used for 4 h daily in astudy, where the lens over the eye with better vision switchedfrom clear to opaque every 30 s (presented at AAO but notpublished). These showed promising results, but commercialapplication of these glasses is still limited.

Interactive Binocular Treatment (I-BiT) for Amblyopia

The I-BiT prototype system was developed as an alternativeto patching treatment and utilized a virtual reality technology.The treatment was designed to appeal to children and thereforeimprove compliance. Computer games and video footage weredisplayed in such a way that the amblyopic eye of a patient could bepreferentially stimulated during binocular viewing conditions.[26]This technology was converted into a computer-based gameand 3D shutter glasses in a study.[27] Patients received 30min ofI-BiT treatment once a week for 6 weeks, giving a maximal totaltreatment time of 3 h. Six of nine patients (67%) who completedthe treatment showed a clinically significant improvement of0.125 LogMAR units or more at follow-up of 10 weeks. Thus,this user-friendly treatment provided a small group showing asignificant improvement which has to be reproduced in otherstudies.

Binocular treatment of amblyopia using video games is anongoing trial to investigate whether 6 weeks of binocular treatmentleads to a greater improvement in amblyopic eye visual acuity than6 weeks of a placebo treatment.[28] The trial will also assess whetherbinocular treatment improves stereopsis and quality of life, andreduces interocular suppression to a greater extent than placebotreatment. In conclusion, current occlusion therapy, althoughefficient in recovering the monocular visual acuity of the amblyopiceye, prevents the two eyes from working together. Newer modelsbelieve, patients with amblyopia may have a structurally intact,but functionally suppressed, binocular visual system. Publishedreports indicate that the learning (or improving) potential is stillpresent in treated amblyopes, who have normal monocular visualacuity and that additional treatment might be necessary. Thecurrent research aims at stimulating binocular interaction. Theproven advantages of the binocular therapies are (1) contrastbalanced binocular treatment improves monocular and binocularvisual function in children and adults, (2) the treatment is rapid,working within a matter of weeks, and (3) the effects last in excessof 1 month after the cessation of treatment.

46 Clinical and Experimental Vision and Eye Research, January-June, Vol 1, 2018

Binocular treatment of amblyopia Kaur and Dadeya

References
  1. Pediatric Eye Disease Investigator Group. The clinical profileof moderate amblyopia in children younger than 7 years. ArchOphthalmol 2002;120:281-7.
  2. Pediatric Eye Disease Investigator Group. The course of moderateamblyopia treated with patching in children: Experience of theamblyopia treatment study. Am J Ophthalmol 2003;136:620-9.
  3. Pediatric Eye Disease Investigator Group, Repka MX, Kraker RT,Beck RW, Holmes JM, Cotter SA, et al. A randomized trial ofatropine vs patching for treatment of moderate amblyopia: Followupat age 10 years. Arch Ophthalmol 2008;126:1039-44.
  4. Scheiman MM, Hertle RW, Kraker RT, Beck RW, Birch EE, Felius J,et al. Patching vs atropine to treat amblyopia in children aged 7 to12 years: A randomized trial. Arch Ophthalmol 2008;126:1634-42.
  5. Scheiman MM, Hertle RW, Beck RW, Edwards AR, Birch E,Cotter SA, et al. Randomized trial of treatment of amblyopia inchildren aged 7 to 17 years. Arch Ophthalmol 2005;123:437-47.
  6. Holmes JM, Beck RW, Kraker RT, Astle WF, Birch EE, Cole SR,et al. Risk of amblyopia recurrence after cessation of treatment.J AAPOS 2004;8:420-8.
  7. Hertle RW, Scheiman MM, Beck RW, Chandler DL, Bacal DA,Birch E, et al. Stability of visual acuity improvement followingdiscontinuation of amblyopia treatment in children aged 7 to12 years. Arch Ophthalmol 2007;125:655-9.
  8. Levi DM, Li RW. Perceptual learning as a potential treatment foramblyopia: A mini-review. Vision Res 2009;49:2535-49.
  9. Polat U, Ma-Naim T, Belkin M, Sagi D. Improving vision in adultamblyopia by perceptual learning. Proc Natl Acad Sci U S A2004;101:6692-7.
  10. Levi DM, Polat U. Neural plasticity in adults with amblyopia. ProcNatl Acad Sci U S A 1996;93:6830-4.
  11. Jeter PE, Dosher BA, Petrov A, Lu ZL. Task precision at transferdetermines specificity of perceptual learning. J Vis 2009;9:1.1-13.
  12. Li RW, Young KG, Hoenig P, Levi DM. Perceptual learning improvesvisual performance in juvenile amblyopia. Invest Ophthalmol Vis Sci2005;46:3161-8.
  13. Polat U, Ma-Naim T, Spierer A. Treatment of children withamblyopia by perceptual learning. Vision Res 2009;49:2599-603.

 
  1. Li RW, Provost A, Levi DM. Extended perceptual learning results insubstantial recovery of positional acuity and visual acuity in juvenileamblyopia. Invest Ophthalmol Vis Sci 2007;48:5046-51.
  2. Hussain Z, Webb BS, Astle AT, McGraw PV. Perceptual learningreduces crowding in amblyopia and in the normal periphery.J Neurosci 2012;32:474-80.
  3. Hess RF, Babu RJ, Clavagnier S, Black J, Bobier W, Thompson B, et al.The iPod binocular home-based treatment for amblyopia in adults:Efficacy and compliance. Clin Exp Optom 2014;97:389-98.
  4. Hess RF, Mansouri B, Thompson B. A new binocular approach tothe treatment of amblyopia in adults well beyond the critical periodof visual development. Restor Neurol Neurosci 2010;28:793-802.
  5. Li J, Thompson B, Deng D, Chan LY, Yu M, Hess RF, et al.Dichoptic training enables the adult amblyopic brain to learn. CurrBiol 2013;23:R308-9.
  6. To L, Thompson B, Blum JR, Maehara G, Hess RF, Cooperstock JR,et al. A game platform for treatment of amblyopia. IEEE TransNeural Syst Rehabil Eng 2011;19:280-9.
  7. Birch EE, Li SL, Jost RM, Morale SE, De La Cruz A, Stager D Jr.,et al. Binocular iPad treatment for amblyopia in preschool children.J AAPOS 2015;19:6-11.
  8. Li SL, Jost RM, Morale SE, Stager DR, Dao L, Stager D, et al.A binocular iPad treatment for amblyopic children. Eye (Lond)2014;28:1246-53.
  9. Holmes JM, Manh VM, Lazar EL, Beck RW, Birch EE, Kraker RT,et al. Effect of a binocular iPad game vs part-time patching inchildren aged 5 to 12 years with amblyopia: A randomized clinicaltrial. JAMA Ophthalmol 2016;134:1391-400.
  10. Manh VM, Holmes JM, Lazar EL, Kraker RT, Wallace DK,Kulp MT, et al. A randomized trial of a binocular iPad game versuspart-time patching in children aged 13 to 16 years with amblyopia.Am J Ophthalmol 2018;186:104-15.
  11. Gao TY, Guo CX, Babu RJ, Black JM, Bobier WR, Chakraborty A,et al. Effectiveness of a binocular video game vs placebo video gamefor improving visual functions in older children, teenagers, and adultswith amblyopia: A Randomized clinical trial. JAMA Ophthalmol2018;136:172-81.
  12. Kelly KR, Jost RM, Doa L, Beauchamp CL, Leffler JN, Birch EE.A randomized trial of a binocular iPod game vs patching for treatmentof amblyopia in children. JAMA Ophthalmol 2016. (In Press).
  13. Eastgate RM, Griffiths GD, Waddingham PE, Moody AD, Butler TK,Cobb SV, et al. Modified virtual reality technology for treatment ofamblyopia. Eye (Lond) 2006;20:370-4.
  14. Herbison N, Cobb S, Gregson R, Ash I, Eastgate R, Purdy J, et al.Interactive binocular treatment (I-biT) for amblyopia: Results of apilot study of 3D shutter glasses system. Eye (Lond) 2013;27:1077-83.
  15. Guo CX, Babu RJ, Black JM, Bobier WR, Lam CS, Dai S, et al.Binocular treatment of amblyopia using videogames (BRAVO):Study protocol for a randomised controlled trial. Trials 2016;17:504.

Clinical and Experimental Vision and Eye Research, January-June, Vol 1, 2018 47