Compromised Integrity of Central Visual Pathways in Patients With Macular Degeneration

Malania, Maka; Konrád, J; Jägle, Herbert; Werner, John S.; Greenlee, Mark W.

doi:10.1167/iovs.16-21191

Cited by 27 publications

(49 citation statements)

References 58 publications

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“…Future higher resolution studies might be able to report such damage. Our results are consistent with recent reports demonstrating that the white matter within the optic radiation is affected by AMD (Malania et al 2017). We go beyond these previous reports by utilizing an anatomically-informed method that allowed us to characterize the specificity of the relation between locations of retinal damage and the visual white matter.…”

Section: Discussionsupporting

confidence: 90%

“…This suggests possible mechanisms for transsynaptic effects from the photoreceptors to the brain tissue. Indeed, our current results, previous ones (Malania et al 2017) as well as results demonstrating a reduction in cortical volume in AMD (Hernowo et al 2014;Prins et al 2016a, b) all provide strong convergent evidence that cell death within the retina could affect the brain tissue via transsynaptic degeneration (Prins et al 2016a;Haak et al 2016).…”

Section: Discussionsupporting

confidence: 85%

“…To do so, we performed an advanced, anatomically precise characterization of the relationship between the locus of retinal damage in AMD (fovea) and the white matter fascicles within the optic radiation projecting to locations of primary visual cortex that represent different eccentricities-fovea, parafoveal and peripheral regions combining anatomical and advanced computational methods (Benson et al 2012(Benson et al , 2014. This fine grade mapping between the retinotopic location of damage and white matter goes beyond previous reports (Prins et al 2016a, b;Hernowo et al 2014;Malania et al 2017). Furthermore, we demonstrate that changes in the microstructural properties of the OR correlate with AMD patients' visual acuity, indicating a relationship between the tissue properties of the OR and the long-term loss in visual function that characterizes AMD.…”

Section: Introductionmentioning

confidence: 91%

“…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). Yet to date, the complete set of mechanisms by which AMD has long-term effects on the human brain and behavior are not well understood.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

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We investigated the impact of age-related macular degeneration (AMD) on visual acuity and the visual white matter. We combined an adaptive cortical atlas and diffusion-weighted magnetic resonance imaging (dMRI) and tractography to separate optic radiation (OR) projections to different retinal eccentricities in human primary visual cortex. We exploited the known anatomical organization of the OR and clinically relevant data to segment the OR into three primary components projecting to fovea, mid-and far-periphery. We measured white matter tissue properties-fractional anisotropy, linearity, planarity, sphericity-along the aforementioned three components of the optic radiation to compare AMD patients and controls. We found differences in white matter properties specific to OR white matter fascicles projecting to primary visual cortex locations corresponding to the location of retinal damage (fovea). Additionally, we show that the magnitude of white matter properties in AMD patients' correlates with visual acuity. In sum, we demonstrate a specific relation between visual loss, anatomical location of retinal damage and white matter damage in AMD patients. Importantly, we demonstrate that these changes are so profound that can be detected using magnetic resonance imaging data with clinical resolution. The conserved mapping between retinal and white matter damage suggests that retinal neurodegeneration might be a primary cause of white matter degeneration in AMD patients. The results highlight the impact of eye disease on brain tissue, a process that may become an important target to monitor during the course of treatment.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 85%

Section: Introductionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

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“…A recent tractography-based study showed similar, significant reductions in optic tract FA as well as correlations between RNFL thickness and optic tract FA in participants with childhood or age-related macular degeneration. 37 These additional ophthalmologic measurements allow for a secondary level of verification of any microstructural abnormalities and provides a more precise mapping of the relationship between the various scales and measures of prethalamic microstructure integrity.…”

Section: Fellow and Affected Eye Optic Nerves In Amblyopiamentioning

confidence: 99%

Retinothalamic White Matter Abnormalities in Amblyopia

Allen

Schmitt

Kushner

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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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 lm 2 /s vs. 0.68 lm 2 /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.

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Comparison of multiple tractography methods for reconstruction of the retinogeniculate visual pathway using diffusion MRI

Zhang

Xie

et al. 2021

Human Brain Mapping

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The retinogeniculate visual pathway (RGVP) conveys visual information from the retina to the lateral geniculate nucleus. The RGVP has four subdivisions, including two decussating and two nondecussating pathways that cannot be identified on conventional structural magnetic resonance imaging (MRI). Diffusion MRI tractography has the potential to trace these subdivisions and is increasingly used to study the RGVP. However, it is not yet known which fiber tracking strategy is most suitable for RGVP reconstruction. In this study, four tractography methods are compared, including constrained spherical deconvolution (CSD) based probabilistic (iFOD1) and deterministic (SD-Stream) methods, and multi-fiber (UKF-2T) and single-fiber (UKF-1T) unscented Kalman filter (UKF) methods. Experiments use diffusion MRI data from 57 subjects in the Human Connectome Project. The RGVP is identified using regions of interest created by two clinical experts. Quantitative anatomical measurements and expert anatomical judgment are used to assess the advantages and limitations of the four tractography methods. Overall, we conclude that UKF-2T and iFOD1 produce the best RGVP reconstruction results. The iFOD1 method can better quantitatively estimate the percentage of decussating fibers, while the UKF-2T method produces reconstructed RGVPs that are judged to better correspond to the known anatomy and have the highest spatial overlap across subjects.Overall, we find that it is challenging for current tractography methods to both accurately Jianzhong He and Fan Zhang are co-first-authors.

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Compromised Integrity of Central Visual Pathways in Patients With Macular Degeneration

Abstract: The results indicate that the RNFL and the white matter of the visual pathways are significantly altered in MD patients. Damage to the photoreceptors in MD leads to atrophy of the ganglion cell axons and to corresponding changes in microstructural properties of central visual pathways.

Cited by 27 publications

References 58 publications

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

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

Retinothalamic White Matter Abnormalities in Amblyopia

Comparison of multiple tractography methods for reconstruction of the retinogeniculate visual pathway using diffusion MRI

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