Eye Movements , Strabismus , Amblyopia and Neuro-Ophthalmology Retinothalamic White Matter Abnormalities in Amblyopia

Purpose Amblyopia is associated with a broad array of perceptual and neural abnormalities in the visual system, particularly in untreated or unsuccessfully treated populations. Traditionally, it has been believed that the neural abnormalities are confined to the visual cortex and subcortex (e.g., lateral geniculate nucleus). Here, we investigate the presence of neuroanatomical abnormalities earlier in the visual stream, in the optic nerves and tracts, of participants with two predominant forms of amblyopia. Methods We used diffusion magnetic resonance imaging and probabilistic tractography to compare the microstructural properties of five white matter visual pathways between 15 participants with amblyopia (eight anisometropic, five strabismic, and two exhibiting both etiologies), and 13 age-matched controls. Results Participants with amblyopia exhibited significantly smaller mean fractional anisotropy in the optic nerve and optic tract (0.26 and 0.31 vs. 0.31 and 0.36 in controls, respectively). We also found greater mean diffusivity in the optic radiation compared to controls (0.72 μm2/s vs. 0.68 μm2/s, respectively). Comparing etiologies, the abnormalities in the precortical pathways tended to be more severe in participants with anisometropic compared to strabismic amblyopia, and anisometropic participants' optic nerves, optic tracts, and optic radiations significantly differed from control participants' (all, P < 0.05). Conclusions The results indicate that amblyopia may be associated with microstructural abnormalities in neural networks as early as the retina, and these abnormalities may differ between amblyopic etiologies.

[1]  Katrin Amunts,et al.  Cortical Folding Patterns and Predicting Cytoarchitecture , 2007, Cerebral cortex.

[2]  E. Wu,et al.  Diffusion Tensor MR Study of Optic Nerve Degeneration in Glaucoma , 2007, 2007 29th Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[3]  Franco Pestilli,et al.  Altered white matter in early visual pathways of humans with amblyopia , 2015, Vision Research.

[4]  P. Basser,et al.  Estimation of the effective self-diffusion tensor from the NMR spin echo. , 1994, Journal of magnetic resonance. Series B.

[5]  J. Horton,et al.  Pattern of ocular dominance columns in human striate cortex in strabismic amblyopia , 1996, Visual Neuroscience.

[6]  Ji Man Park,et al.  The Analysis of Peripapillary RNFL, Macula and Macular Ganglion Cell Layer Thickness in Patients with Monocular Amblyopia Using SD-OCT , 2016 .

[7]  P. Basser,et al.  In vivo fiber tractography using DT‐MRI data , 2000, Magnetic resonance in medicine.

[8]  P. Lempert Retinal area and optic disc rim area in amblyopic, fellow, and normal hyperopic eyes: a hypothesis for decreased acuity in amblyopia. , 2008, Ophthalmology.

[9]  J Anthony Movshon,et al.  The pattern of visual deficits in amblyopia. , 2003, Journal of vision.

[10]  Kyoung-Min Lee,et al.  Comparison between anisometropic and strabismic amblyopia using functional magnetic resonance imaging , 2001, The British journal of ophthalmology.

[11]  L Tychsen,et al.  Nasotemporal asymmetries in V1: Ocular dominance columns of infant, adult, and strabismic macaque monkeys , 1997, The Journal of comparative neurology.

[12]  J. Féher,et al.  Age-related changes in the human optic nerve. , 2002, Canadian journal of ophthalmology. Journal canadien d'ophtalmologie.

[13]  Shu-Wei Sun,et al.  Diffusion tensor imaging detects and differentiates axon and myelin degeneration in mouse optic nerve after retinal ischemia , 2003, NeuroImage.

[14]  G. V. von Noorden,et al.  Histological studies of the visual system in monkeys with experimental amblyopia. , 1973, Investigative ophthalmology.

[15]  D. Levi Linking assumptions in amblyopia , 2013, Visual Neuroscience.

[16]  G. K. Noorden Histological Studies of the Visual System in Monkeys with Experimental Amblyopia , 1973 .

[17]  Mark W. Woolrich,et al.  Advances in functional and structural MR image analysis and implementation as FSL , 2004, NeuroImage.

[18]  Serge O Dumoulin,et al.  Decreased gray matter concentration in the lateral geniculate nuclei in human amblyopes. , 2010, Investigative ophthalmology & visual science.

[19]  John S Werner,et al.  Compromised Integrity of Central Visual Pathways in Patients With Macular Degeneration. , 2017, Investigative ophthalmology & visual science.

[20]  A. Norcia,et al.  The Structural Properties of Major White Matter Tracts in Strabismic Amblyopia. , 2015, Investigative ophthalmology & visual science.

[21]  D. Hubel,et al.  The period of susceptibility to the physiological effects of unilateral eye closure in kittens , 1970, The Journal of physiology.

[22]  D. Hubel,et al.  Plasticity of ocular dominance columns in monkey striate cortex. , 1977, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[23]  W. Green,et al.  Optic nerve damage in human glaucoma. III. Quantitative correlation of nerve fiber loss and visual field defect in glaucoma, ischemic neuropathy, papilledema, and toxic neuropathy. , 1982, Archives of ophthalmology.

[24]  M Schulzer,et al.  The effect of age on the nerve fiber population of the human optic nerve. , 1984, American journal of ophthalmology.

[25]  F. Garaci,et al.  Differences between proximal versus distal intraorbital optic nerve diffusion tensor magnetic resonance imaging properties in glaucoma patients. , 2012, Investigative ophthalmology & visual science.

[26]  J. Horton,et al.  Pattern of ocular dominance columns and cytochrome oxidase activity in a macaque monkey with naturally occurring anisometropic amblyopia , 1997, Visual Neuroscience.

[27]  P. Lempert Optic nerve hypoplasia and small eyes in presumed amblyopia. , 2000, Journal of AAPOS : the official publication of the American Association for Pediatric Ophthalmology and Strabismus.

[28]  Ching-Yu Cheng,et al.  Retinal nerve fiber layer thickness in unilateral amblyopia. , 2004, Investigative ophthalmology & visual science.

[29]  P. Lempert,et al.  Dysversion of the optic disc and axial length measurements in a presumed amblyopic population. , 1998, Journal of AAPOS : the official publication of the American Association for Pediatric Ophthalmology and Strabismus.

[30]  Amblyopia induced by anisometropia without shrinkage of ocular dominance columns in human striate cortex. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[31]  Stefan Skare,et al.  How to correct susceptibility distortions in spin-echo echo-planar images: application to diffusion tensor imaging , 2003, NeuroImage.

[32]  Nikos Makris,et al.  Automatically parcellating the human cerebral cortex. , 2004, Cerebral cortex.

[33]  J. Jonas,et al.  Histomorphometry of the human optic nerve. , 1990, Investigative ophthalmology & visual science.

[34]  Nicoletta Berardi,et al.  Reducing Intracortical Inhibition in the Adult Visual Cortex Promotes Ocular Dominance Plasticity , 2010, The Journal of Neuroscience.

[35]  Kenneth K Kwong,et al.  Voxel‐based analysis of MRI detects abnormal visual cortex in children and adults with amblyopia , 2005, Human brain mapping.

[36]  A. Flanders Optic Nerve and Optic Radiation Neurodegeneration in Patients with Glaucoma: In Vivo Analysis with 3-T Diffusion-Tensor MR Imaging , 2010 .

[37]  H A Quigley,et al.  The effect of age on normal human optic nerve fiber number and diameter. , 1989, Ophthalmology.

[38]  B J Kushner,et al.  Functional amblyopia associated with abnormalities of the optic nerve. , 1984, Archives of ophthalmology.

[39]  J. Kiryu,et al.  A comparison between amblyopic and fellow eyes in unilateral amblyopia using spectral-domain optical coherence tomography , 2014, Clinical ophthalmology.

[40]  D. Hubel,et al.  The development of ocular dominance columns in normal and visually deprived monkeys , 1980, The Journal of comparative neurology.