The Structural Properties of Major White Matter Tracts in Strabismic Amblyopia

Abstract

PURPOSE. In order to better understand whether white matter structural deficits are present in strabismic amblyopia, we performed a survey of the tissue properties of 28 major white matter tracts using diffusion and quantitative magnetic resonance imaging approaches.METHODS. We used diffusion-based tensor modeling and a new quantitative T1 protocol to measure fractional anisotropy (FA), mean diffusivity (MD), and myelin-sensitive T1 values. We surveyed tracts in the occipital lobe, including the vertical occipital fasciculus (VOF)-a newly rediscovered tract that bridges dorsal and ventral areas of the occipital lobe, as well as tracts across the rest of the brain. RESULTS.Adults with long-standing strabismic amblyopia show tract-specific elevations in MD. We rank-ordered the tracts on the basis of their MD effect-size. The four most affected tracts were the anterior frontal corpus callosum (ACC), the right VOF, the left inferior longitudinal fasciculus (ILF) and the left optic radiation. CONCLUSIONS.The results suggest that most white matter tissue properties are relatively robust to the early visual insult caused by strabismus. However, strabismic amblyopia does affect MD, not only in occipital tracts, such as the VOF and optic radiation, but also in long range association tracts connecting visual cortex to the frontal and temporal lobes (ILF) and connecting the two hemispheres (ACC).

Retinothalamic White Matter Abnormalities in Amblyopia

“…4,7,8 The magnitude of the increase in mean diffusivity of the optic radiation was roughly consistent with our previous study (about 10% greater compared to controls). We previously suggested this finding provides cursory evidence of a feedback, rather than feedforward, model of cortical abnormality in amblyopia.…”

“…This is not to suggest visual corticocortical white matter is unaffected per se in amblyopia, since similar recent studies have shown abnormalities in late-stream occipital projections such as the vertical occipital fasciculus, occipitofrontal projections such as the inferior longitudinal fasciculus, and interhemispheric connections in the anterior frontal corpus callosum. 8 Additionally, behavioral deficits such as difficulty inferring form from motion suggest amblyopia is associated with functional abnormalities more complex than can be explained by imbalanced binocular integration in thalamus and primary visual cortex. Without a more comprehensive cross-subject tractographic mapping of visual system white matter architecture, it is unclear the extent to which corticocortical pathway abnormalities reflect genuine differences versus overlap with voxels containing abnormal thalamocortical axons.…”

“…[4][5][6] Visual white matter is also abnormal in amblyopia, particularly in fascicles connecting the thalamus to the visual (striate and extrastriate) cortex, such as the optic radiation. 7,8 These structural abnormalities appear to have downstream consequences, affecting not only the way visual information is processed in the cortex but also how that information is integrated in thalamocortical feedback networks. These abnormalities can vary by etiology and sometimes scale with the degree of perceptual loss, although these relationships are not always clear.…”

Age-related macular degeneration affects the optic radiation white matter projecting to locations of retinal damage

“…1-2). We measured the white matter tissue along the OT and OR using tract profiles (Yeatman et al 2012;Ogawa et al 2014;Allen et al 2015;Ajina et al 2015;Duan et al 2015;Gomez et al 2015;Leong et al 2016;Libero et al 2016) and the tensor model (Basser and Jones 2002;Basser and Pierpaoli 1998). Supplementary Fig.…”

“…For example, the human white matter is affected during normal aging as well as in age-related diseases, such as Alzheimer's or progressive cognitive degeneration (Mayda et al 2010;Wang et al 2010Wang et al , 2012Yeatman et al 2014; Thomason and Thompson 2011). The visual white matter pathways have been also shown to be affected by visual and eye disease, for example, developmental prosopagnosia (Gomez et al 2015;Thomas et al 2008), amblyopia (Allen et al 2015(Allen et al , 2018Duan et al 2015), and retinal ganglion cell damage (Ogawa et al 2014) have all been reported to affect properties of the human white matter, please see Ariel Rokem et al 2017;Millington et al 2014 for reviews. Evidence from in vivo studies suggest that macular degeneration also affects volume of the human primary visual cortex and the visual pathways (Prins et al 2016a, b;Hernowo et al 2014;Malania et al 2017).…”