Amblyopia

In this rural Chinese population, 2.8% of adults 30 to 80 years of age had amblyopia, a prevalence rate broadly consistent with that of most other studies. One third of the cases were bilateral, and anisometropia was the most common cause of this condition.{Wang Y, Liang YB, Sun LP, Duan XR, Yuan RZ, Wong TY, Yi P, Friedman DS, Wang NL, Wang JJ. Prevalence and causes of amblyopia in a rural adult population of Chinese the Handan Eye Study. Ophthalmology. 2011 Feb;118(2):279-83.}

In a randomised controlled trial comparing intensive orthoptic screening at 8, 12, 18, 25, 31, and 37 months (intensive group) with orthoptic screening at 37 months only (control group), the intensive orthoptic screening protocol was associated with better acuity in the amblyopic eye and a lower prevalence of amblyopia at 7.5 years of age, in comparison with screening at 37 months only. These data support the hypothesis that early treatment for amblyopia leads to a better outcome than later treatment and may act as a stimulus for research into feasible screening programmes.{Williams C, Northstone K, Harrad RA, Sparrow JM, Harvey I; ALSPAC Study Team. Amblyopia treatment outcomes after screening before or at age 3 years: follow up from randomised trial. BMJ. 2002 Jun 29;324(7353):1549.}

In view of the spectrum of critical windows for different visual functions and for different types of amblyopia, combined with individual variability in these windows, treatment of amblyopia has been increasingly offered to older children and adults.{Holmes JM, Levi DM. Treatment of amblyopia as a function of age. Vis Neurosci. 2018 Jan;35:E015.}

Using a combination of psychophysical, electrophysiological, imaging, risk factor analysis, and fine motor skill assessment, the primary role of binocular dysfunction in the genesis of amblyopia and the constellation of visual and motor deficits that accompany the visual acuity deficit has been identified. These findings motivated us to evaluate a new, binocular approach to amblyopia treatment with the goals of reducing or eliminating residual and recurrent amblyopia and of improving the deficient ocular motor function and fine motor skills that accompany amblyopia.{Birch EE. Amblyopia and binocular vision. Prog Retin Eye Res. 2013 Mar;33:67-84.}

The frequent co-existence of amblyopia and anisometropia at a child’s first clinical examination promotes the belief that the anisometropia has caused the amblyopia, as has been demonstrated in animal models of the condition. In reviewing the human and monkey literature however it is clear that there are additional paths beyond this classic hypothesis to the co-occurrence of anisometropia and amblyopia.{Barrett BT, Bradley A, Candy TR. The relationship between anisometropia and amblyopia. Prog Retin Eye Res. 2013 Sep;36:120-58.}

The mainstay of treatment for amblyopia has been based on increasing visual stimulation of the amblyopic eye by occlusion, atropine, or optical penalization of the dominant eye. It has been established that refractive adaptation alone can significantly enhance visual acuity. However, the duration of optical correction varies between studies and the effectiveness of spectacle wear over early beginning of patching is still under investigation.{Papageorgiou E, Asproudis I, Maconachie G, Tsironi EE, Gottlob I. The treatment of amblyopia: current practice and emerging trends. Graefes Arch Clin Exp Ophthalmol. 2019 Jun;257(6):1061-1078.}

Early work on perceptual learning as well as more recent enthusiasm for iPad-based dichoptic training have each generated interesting and promising data for vision improvement in amblyopes. Use of pharmaceutical augmentation of traditional therapies has also been investigated. Several different drugs with unique mechanisms of action are thought to be able to neurosensitise the brain and enhance responsiveness to amblyopia therapy.{Kraus CL, Culican SM. New advances in amblyopia therapy I: binocular therapies and pharmacologic augmentation. Br J Ophthalmol. 2018 Nov;102(11):1492-1496.}

There is no level I evidence to support the use of binocular treatment as a substitute for current therapies for amblyopia (including patching and optical treatment). Furthermore, 2 large randomized controlled trials showed inferior performance compared with standard patching treatment. On the basis of this review of the published literature, binocular therapy cannot be recommended as a replacement for standard amblyopia therapy.{Pineles SL, Aakalu VK, Hutchinson AK, Galvin JA, Heidary G, Binenbaum G, VanderVeen DK, Lambert SR. Binocular Treatment of Amblyopia: A Report by the American Academy of Ophthalmology. Ophthalmology. 2020 Feb;127(2):261-272.}

In children aged 7 to 12 years who have received previous treatment for amblyopia other than spectacles, there was no benefit to VA or stereoacuity from 4 or 8 weeks of treatment with the dichoptic binocular Dig Rush iPad game.{Pediatric Eye Disease Investigator Group, Holmes JM, Manny RE, Lazar EL, Birch EE, Kelly KR, Summers AI, Martinson SR, Raghuram A, Colburn JD, Law C, Marsh JD, Bitner DP, Kraker RT, Wallace DK. A Randomized Trial of Binocular Dig Rush Game Treatment for Amblyopia in Children Aged 7 to 12 Years. Ophthalmology. 2019 Mar;126(3):456-466.}

The specific home-based binocular falling-blocks video game used in this clinical trial of individuals 7 years and older with unilateral amblyopia did not improve visual outcomes more than the placebo video game despite increases in fellow eye contrast during game play.{Gao TY, Guo CX, Babu RJ, Black JM, Bobier WR, Chakraborty A, Dai S, Hess RF, Jenkins M, Jiang Y, Kearns LS, Kowal L, Lam CSY, Pang PCK, Parag V, Pieri R, Raveendren RN, South J, Staffieri SE, Wadham A, Walker N, Thompson B; BRAVO Study Team. Effectiveness of a Binocular Video Game vs Placebo Video Game for Improving Visual Functions in Older Children, Teenagers, and Adults With Amblyopia: A Randomized Clinical Trial. JAMA Ophthalmol. 2018 Feb 1;136(2):172-181.}

In teenagers aged 13 to <17 years, improvement in amblyopic eye VA with the binocular iPad game used in this study was not found to be better than patching, and was possibly worse.{Manh VM, Holmes JM, Lazar EL, Kraker RT, Wallace DK, Kulp MT, Galvin JA, Shah BK, Davis PL; Pediatric Eye Disease Investigator Group. A Randomized Trial of a Binocular iPad Game Versus Part-Time Patching in Children Aged 13 to 16 Years With Amblyopia. Am J Ophthalmol. 2018 Feb;186:104-115.}

In children aged 5 to younger than 13 years, amblyopic-eye VA improved with binocular game play and with patching, particularly in younger children (age 5 to <7 years) without prior amblyopia treatment. Although the primary noninferiority analysis was indeterminate, a post hoc analysis suggested that VA improvement with this particular binocular iPad treatment was not as good as with 2 hours of prescribed daily patching.{Holmes JM, Manh VM, Lazar EL, Beck RW, Birch EE, Kraker RT, Crouch ER, Erzurum SA, Khuddus N, Summers AI, Wallace DK; Pediatric Eye Disease Investigator Group. Effect of a Binocular iPad Game vs Part-time Patching in Children Aged 5 to 12 Years With Amblyopia: A Randomized Clinical Trial. JAMA Ophthalmol. 2016 Dec 1;134(12):1391-1400.}

In a randomized controlled trial of binocular iPad game vs patching in children with amblyopia, the iPad game was more efficacious than patching at the 2-week visit. At the 4-week visit, no group difference was found in BCVA change.{Kelly KR, Jost RM, Dao L, Beauchamp CL, Leffler JN, Birch EE. Binocular iPad Game vs Patching for Treatment of Amblyopia in Children: A Randomized Clinical Trial. JAMA Ophthalmol. 2016 Dec 1;134(12):1402-1408.}

Visual acuity improved over 8 weeks in children with unilateral deprivation amblyopia who played a binocular contrast-rebalanced binocular iPad game.{Birch EE, Jost RM, Wang SX, Kelly KR. A pilot randomized trial of contrast-rebalanced binocular treatment for deprivation amblyopia. J AAPOS. 2020 Dec;24(6):344.e1-344.e5.}

Long term follow-up of a randomized clinical trial showed improvements with amblyopia treatment were maintained at 15 years of age, with similar outcomes in both groups.{Repka MX, Kraker RT, Holmes JM, Summers AI, Glaser SR, Barnhardt CN, Tien DR; Pediatric Eye Disease Investigator Group. Atropine vs patching for treatment of moderate amblyopia: follow-up at 15 years of age of a randomized clinical trial. JAMA Ophthalmol. 2014 Jul;132(7):799-805.}

Atropine or patching resulted in similar visual improvement in the amblyopic eye at 2 years.{Repka MX, Wallace DK, Beck RW, Kraker RT, Birch EE, Cotter SA, Donahue S, Everett DF, Hertle RW, Holmes JM, Quinn GE, Scheiman MM, Weakley DR; Pediatric Eye Disease Investigator Group. Two-year follow-up of a 6-month randomized trial of atropine vs patching for treatment of moderate amblyopia in children. Arch Ophthalmol. 2005 Feb;123(2):149-57.}

Atropine or patching resulted in similar visual improvement in the amblyopic eye at 17 weeks. {Scheiman MM, Hertle RW, Kraker RT, Beck RW, Birch EE, Felius J, Holmes JM, Kundart J, Morrison DG, Repka MX, Tamkins SM; Pediatric Eye Disease Investigator Group. Patching vs atropine to treat amblyopia in children aged 7 to 12 years: a randomized trial. Arch Ophthalmol. 2008 Dec;126(12):1634-42.}

Weekend atropine can improve visual acuity in children 3 to 12 years of age with severe amblyopia.{Repka MX, Kraker RT, Beck RW, Birch E, Cotter SA, Holmes JM, Hertle RW, Hoover DL, Klimek DL, Marsh-Tootle W, Scheiman MM, Suh DW, Weakley DR; Pediatric Eye Disease Investigator Group. Treatment of severe amblyopia with weekend atropine: results from 2 randomized clinical trials. J AAPOS. 2009 Jun;13(3):258-63.}

Combined atropine and patching therapy resulted in more mean improvement of amblyopic eye VA than patching alone at 6 months (7.2 lines vs 5.8 lines).{Wang S, Wen W, Zhu W, Liu Y, Zou L, Tian T, Lin J, Liu R, Liu H. Effect of Combined Atropine and Patching vs Patching Alone for Treatment of Severe Amblyopia in Children Aged 3 to 12 Years: A Randomized Clinical Trial. JAMA Ophthalmol. 2021 Sep 1;139(9):990-996.}

When amblyopic eye VA stops improving with 2 hours of daily patching, increasing the daily patching dosage to 6 hours results in more improvement in VA after 10 weeks compared with continuing 2 hours daily.{Pediatric Eye Disease Investigator Group, Wallace DK, Lazar EL, Holmes JM, Repka MX, Cotter SA, Chen AM, Kraker RT, Beck RW, Clarke MP, Lorenzana IJ, Petersen DB, Roberts JT, Suh DW. A randomized trial of increasing patching for amblyopia. Ophthalmology. 2013 Nov;120(11):2270-7.}

Following a period of treatment with spectacles, 2 hours of daily patching combined with 1 hour of near visual activities improved vision in the amblyopic eye further by around 1.1 lines at 5 weeks (vs 0.5 lines in control).{Wallace DK; Pediatric Eye Disease Investigator Group, Edwards AR, Cotter SA, Beck RW, Arnold RW, Astle WF, Barnhardt CN, Birch EE, Donahue SP, Everett DF, Felius J, Holmes JM, Kraker RT, Melia M, Repka MX, Sala NA, Silbert DI, Weise KK. A randomized trial to evaluate 2 hours of daily patching for strabismic and anisometropic amblyopia in children. Ophthalmology. 2006 Jun;113(6):904-12.}

Compliance with patching treatment averages less than 50% and is influenced by several factors.{Wallace MP, Stewart CE, Moseley MJ, Stephens DA, Fielder AR; Monitored Occlusion Treatment Amblyopia Study (MOTAS) Cooperatives; Randomized Occlusion Treatment Amblyopia Study (ROTAS) Cooperatives. Compliance with occlusion therapy for childhood amblyopia. Invest Ophthalmol Vis Sci. 2013 Sep 17;54(9):6158-66.}

In a comparative, interventional case series of amblyopic adults treated with eye patching vs prosthetic occluding contact lenses (OCLs), significant improvements in pre- to postamblyopic therapy BCVA were seen at 1.5 months in both groups.{Garcia-Romo E, Perez-Rico C, Roldán-Díaz I, Arévalo-Serrano J, Blanco R. Treating amblyopia in adults with prosthetic occluding contact lenses. Acta Ophthalmol. 2018 May;96(3):e347-e354.}

Optical treatment of amblyopia resulted in a large positive effect size of 1.07 on visual acuity, although the heterogeneity was significant. Meta-regression indicated that effect sizes significantly decreased with age, increased with treatment duration, and that better initial acuity was associated with higher effect sizes.{Asper L, Watt K, Khuu S. Optical treatment of amblyopia: a systematic review and meta-analysis. Clin Exp Optom. 2018 Jul;101(4):431-442.}

Amblyopia improved with optical correction by ≥2 lines in 77% of the patients and resolved in 27% of children aged 3 to <7 years old with untreated anisometropic amblyopia.{Cotter SA; Pediatric Eye Disease Investigator Group, Edwards AR, Wallace DK, Beck RW, Arnold RW, Astle WF, Barnhardt CN, Birch EE, Donahue SP, Everett DF, Felius J, Holmes JM, Kraker RT, Melia M, Repka MX, Sala NA, Silbert DI, Weise KK. Treatment of anisometropic amblyopia in children with refractive correction. Ophthalmology. 2006 Jun;113(6):895-903.}

In a small sample of subjects (20) at the end point of their amblyopia therapy randomized into abrupt cessation vs therapy tapering, there was a 24% risk of amblyopia recurrence if therapy was discontinued abruptly or tapered in 8 weeks. The assigned cessation method did not affect the rate of amblyopia recurrence.{Walsh LA, Hahn EK, LaRoche GR. The method of treatment cessation and recurrence rate of amblyopia. Strabismus. 2009 Sep;17(3):107-16.}

Approximately one fourth of successfully treated amblyopic children experience a recurrence within the first year off treatment. For patients treated with 6 or more hours of daily patching, our data suggest that the risk of recurrence is greater when patching is stopped abruptly rather than when it is reduced to 2 hours per day prior to cessation.{Holmes JM, Beck RW, Kraker RT, Astle WF, Birch EE, Cole SR, Cotter SA, Donahue S, Everett DF, Hertle RW, Keech RV, Paysse E, Quinn GF, Repka MX, Scheiman MM; Pediatric Eye Disease Investigator Group. Risk of amblyopia recurrence after cessation of treatment. J AAPOS. 2004 Oct;8(5):420-8.}

Patients who had amblyopia treatment with patching or atropine for 6 months followed by standard clinical care were found to have similar rates of deterioration and improvement of ocular alignment.{Repka MX, Holmes JM, Melia BM, Beck RW, Gearinger MD, Tamkins SM, Wheeler DT; Pediatric Eye Disease Investigator Group. The effect of amblyopia therapy on ocular alignment. J AAPOS. 2005 Dec;9(6):542-5.}