Amblyopia: neural basis and therapeutic approaches

Bretas, Caio César Peixoto; Soriano, Renato Nery

doi:10.5935/0004-2749.20160099

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Review Articles • Arq. Bras. Oftalmol. 79 (5) • Sep-Oct 2016 • https://doi.org/10.5935/0004-2749.20160099 copy

Amblyopia: neural basis and therapeutic approaches

Ambliopia: bases neurais e intervenções terapêuticas

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Abnormalities in visual processing caused by visual deprivation or abnormal binocular interaction may induce amblyopia, which is characterized by reduced visual acuity. Occlusion therapy, the conventional treatment, requires special attention as occlusion of the fellow normal eye may reduce its visual acuity and impair binocular vision. Besides recovering visual acuity, some researchers have recommended restoration of stereoacuity and motor fusion and reverse suppression in order to prevent diplopia. Recent studies have documented that the amblyopic visual cortex has a normal complement of cells but reduced spatial resolution and a disordered topographical map. Changes occurring in the late sensitive period selectively impact the parvocellular pathway. Distinct morphophysiologic and psychophysical deficits may demand individualization of therapy, which might provide greater and longer-lasting residual plasticity in some children.

Keywords:
Amblyopia; Visual acuity; Neural plasticity; Visual córtex

	Early sensitive period	Late sensitive period
Duration	4 to 18 months of age^a a the age ratio of 1:4 has been considered to compare the relative timing in monkey and man, so that 1 week in the monkey is approximately equivalent to 4 weeks in man (¹⁷17 Davis AR, Sloper JJ, Neveu MM, Hogg CR, Morgan MJ, Holder GE. Electrophysiological and psychophysical differences between early-and late-onset strabismic amblyopia. Invest Ophthalmol Vis Sci. 2003;44(2):610-7.⁾	18 months to 7 years of age^a a the age ratio of 1:4 has been considered to compare the relative timing in monkey and man, so that 1 week in the monkey is approximately equivalent to 4 weeks in man (¹⁷17 Davis AR, Sloper JJ, Neveu MM, Hogg CR, Morgan MJ, Holder GE. Electrophysiological and psychophysical differences between early-and late-onset strabismic amblyopia. Invest Ophthalmol Vis Sci. 2003;44(2):610-7.⁾
Predominant mechanism in binocular connections	Competition^b b outcomes from studies in monkeys; (²¹21 Sloper JJ. Edridge-Green Lecture: Competition and cooperation in visual development. Eye (Lond).1993;7(Pt 3):319-31.⁾	Cooperation^b b outcomes from studies in monkeys; (²¹21 Sloper JJ. Edridge-Green Lecture: Competition and cooperation in visual development. Eye (Lond).1993;7(Pt 3):319-31.⁾
Ocular dominance columns	Under development^b b outcomes from studies in monkeys; (⁴⁶46 LeVay S, Wiesel TN, Hubel DH. The development of ocular dominance columns in normal and visually deprived monkeys. J Comp Neurol. 1980;191(1):1-51.^,⁶⁸68 Hubel DH, Wiesel TN, LeVay S. Plasticity of ocular dominance columns in monkey striate cortex. Philos Trans R Soc Lond B Biol Sci. 1977;278(961):377-409.⁾	Already developed^b b outcomes from studies in monkeys; (⁴⁶46 LeVay S, Wiesel TN, Hubel DH. The development of ocular dominance columns in normal and visually deprived monkeys. J Comp Neurol. 1980;191(1):1-51.^,⁶⁸68 Hubel DH, Wiesel TN, LeVay S. Plasticity of ocular dominance columns in monkey striate cortex. Philos Trans R Soc Lond B Biol Sci. 1977;278(961):377-409.⁾
Occlusion	Hypertrophy of LGN^c c LGN, lateral geniculate nucleus of the thalamus; cells of the non-occluded eye; shrinkage of LGN cells of the occluded eye^b b outcomes from studies in monkeys; (⁶⁹69 Headon MP, Sloper JJ, Hiorns RW, Powell TP. Effects of monocular closure at different ages on deprived and undeprived cells in the primate lateral geniculate nucleus. Brain Res. 1985;350(1-2):57-78. 70 Headon M, Sloper JJ, Hiorns RW, Powell TP. Sizes of neurons in the primate lateral geniculate nucleus during normal development. Brain Res. 1985;350(1-2):51-6.^-⁷¹71 O'Kusky J, Colonnier M. Postnatal changes in the number of neurons and synapses in the visual cortex (area 17) of the macaque monkey: a stereological analysis in normal and monocularly deprived animals. J Comp Neurol. 1982;210(3):291-306.⁾	Selective shrinkage of cells in the parvocellular pathway in both non-occluded and occluded eyes^b b outcomes from studies in monkeys; . Normal size of the magnocellular cells^b b outcomes from studies in monkeys; (⁶⁹69 Headon MP, Sloper JJ, Hiorns RW, Powell TP. Effects of monocular closure at different ages on deprived and undeprived cells in the primate lateral geniculate nucleus. Brain Res. 1985;350(1-2):57-78. 70 Headon M, Sloper JJ, Hiorns RW, Powell TP. Sizes of neurons in the primate lateral geniculate nucleus during normal development. Brain Res. 1985;350(1-2):51-6.^-⁷¹71 O'Kusky J, Colonnier M. Postnatal changes in the number of neurons and synapses in the visual cortex (area 17) of the macaque monkey: a stereological analysis in normal and monocularly deprived animals. J Comp Neurol. 1982;210(3):291-306.⁾
Functional impairment	Parvocellular-related function is more diminished in both the amblyopic and fellow eyes of early and late onset^d d outcomes from human studies. (⁷²72 Davis AR, Sloper JJ, Neveu MM, Hogg CR, Morgan MJ, Holder GE. Differential changes of magnocellular and parvocellular visual function in early- and late-onset strabismic amblyopia. Invest Ophthalmol Vis Sci. 2006;47(11):4836-41.⁾	Parvocellular-related function is more diminished in the amblyopic eye of late-onset subjects^d d outcomes from human studies. (⁷²72 Davis AR, Sloper JJ, Neveu MM, Hogg CR, Morgan MJ, Holder GE. Differential changes of magnocellular and parvocellular visual function in early- and late-onset strabismic amblyopia. Invest Ophthalmol Vis Sci. 2006;47(11):4836-41.⁾

Treatment	Neurophysiologic effects	Disadvantages
Occlusion	Stimulates amblyopic eye, improving its visual acuity by plasticity⁽⁴⁰40 Arakaki MR, Schellini SA, Heimbeck FG, Padovanni CR. Adesão ao tratamento da ambliopia. Arq Bras Oftalmol. 2004;67(2):201-5.⁾	Reduces binocular function⁽³²32 Sperandio AM. Promoção da saúde ocular e prevenção precoce de problemas visuais nos serviços de saúde pública. Rev Saúde Públ. 1999;33(5):513-20.⁾, changes family routine⁽⁴⁹49 Mendonca RH, Ferreira EL. Visual evoked potentials (VEP) and visual acuity improvement after cytidine 52-diphosphocholine (CDP-Choline) therapy in amblyopic patient. Rev Bras Oftalmol. 2012;71(5):328-30.⁾, may induce psychological problems⁽³²32 Sperandio AM. Promoção da saúde ocular e prevenção precoce de problemas visuais nos serviços de saúde pública. Rev Saúde Públ. 1999;33(5):513-20.⁾. Adherence varies⁽²⁶26 Simons K. Amblyopia characterization, treatment, and prophylaxis. Surv Ophthalmol. 2005;50(2):123-66.^,³¹31 Alburquerque RC, Alves, JG. Afecções oculares prevalentes em crianças de baixa renda atendidas em um serviço oftalmológico na cidade do Recife - PE, Brasil. Arq Bras Oftalmol. 2003;66(6):831-4.⁾
Occlusion + perceptual learning	Improves binocular, spatial, and timing functions⁽³²32 Sperandio AM. Promoção da saúde ocular e prevenção precoce de problemas visuais nos serviços de saúde pública. Rev Saúde Públ. 1999;33(5):513-20.⁾	Requires the child’s attentiveness and cooperation⁽⁵⁰50 Levi DM, Li RD. Perceptual learning as a potential treatment for amblyopia: A mini-review. Vision Res. 2009;49(21):2535-49.⁾
Occlusion + levodopa	Increases cortical plasticity⁽³³33 Rezende MS, Souza SB, Dib O, Branzoni E, Ribeiro LE. Abordagem da catarata congênita: análise de série de casos. Rev Bras Oftalmol. 2008;67(1):32-8.⁾	Long-term outcomes need to be monitored⁽³³33 Rezende MS, Souza SB, Dib O, Branzoni E, Ribeiro LE. Abordagem da catarata congênita: análise de série de casos. Rev Bras Oftalmol. 2008;67(1):32-8.⁾
Occlusion + citicoline	Improves action potential conduction⁽³³33 Rezende MS, Souza SB, Dib O, Branzoni E, Ribeiro LE. Abordagem da catarata congênita: análise de série de casos. Rev Bras Oftalmol. 2008;67(1):32-8.⁾	Long-term outcomes need to be monitored⁽³³33 Rezende MS, Souza SB, Dib O, Branzoni E, Ribeiro LE. Abordagem da catarata congênita: análise de série de casos. Rev Bras Oftalmol. 2008;67(1):32-8.⁾
Atropine	Prevents fellow normal eye accommodation, stimulating the amblyopic one⁽⁴⁵45 McCoy PA, Huang H, Philpot BD. Advances in understanding visual cortex plasticity. Curr Opin Neurobiol. 2009;19(3):298-304.⁾	Occlusion outcomes are faster⁽⁴⁵45 McCoy PA, Huang H, Philpot BD. Advances in understanding visual cortex plasticity. Curr Opin Neurobiol. 2009;19(3):298-304.⁾

	Striate cortex (V1)	Extrastriate cortex (V2 and V3)
Complement of cells	Normal	Normal
Spatial resolution	Reduced	Reduced
Cortical magnification factor	Normal	Normal
Topographical map	Disordered	Very disordered
Population receptive field size	Enlarged	Very enlarged

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[1] Corresponding author: Renato Nery Soriano. Setor de Fisiologia e Biofísica. Departamento de Ciências Básicas da Vida. Universidade Federal de Juiz de Fora, Governador Valadares, MG - 35010-177 - Brazil - E-mail: renato.soriano@ufjf.edu.br