Neuroanatomical changes in patients with loss of visual function

Eye diseases that cause loss of visual function are associated with changes in the brain. However, the underlying mechanism of this association is still unclear. Research into this association is important, since the remaining capacity of the brain to conduct and process the input from the eye is believed to be a crucial factor that can affect the success of future vision restoration treatments. Moreover, such research can provide information for a better understanding of the origin of the investigated eye disease. The aim of this thesis was to discover which mechanisms could explain the association between loss of visual function and changes in the brain in general. To investigate this, I studied changes in the brain in various eye diseases that cause visual deprivation. In conclude that changes in the brain – due to loss of visual input – plays an important role in all of the cases. Furthermore, I found evidence that suggests that the eye diseases primary open angle glaucoma and age-related macular degeneration are part of a more general neurodegenerative disorder. This can give directions to future research on the treatment of the eye disease, which might have to expand its focus from treatment of the eye alone towards treatment of both the eye and brain

Loss of Binocular Vision in Monocularly Blind Patients Causes Selective Degeneration of the Superior Lateral Occipital Cortices

PURPOSE. Chronic ocular pathology, such as glaucoma and macular degeneration, is associated with neuroanatomic changes in the visual pathways. It is a challenge to determine the mechanism responsible for these changes. This could be functional deprivation or transsynaptic degeneration. Acquired monocular blindness provides a unique opportunity to establish which mechanism underlies neuroanatomic changes in ocular pathology in general, since the loss of input is well defined, and it causes selective functional deprivation due to the loss of stereopsis. Here, we assessed whether acquired monocular blindness is associated with neuroanatomic changes, and if so, where these changes are located. METHODS. High-resolution T1-weighted magnetic resonance images were obtained in 15 monocularly blind patients and 18 healthy controls. We used voxel-and surface-based morphometry to compare gray and white matter volume, cortical thickness, mean curvature, and surface area between these groups. RESULTS. The gray matter volume in the bilateral superior lateral occipital cortices was decreased in the monocular blind patients, in the absence of volumetric differences in their early visual cortex. CONCLUSIONS. The volumetric decrease in the superior lateral occipital cortices is consistent with specific functional deprivation, as the superior lateral occipital cortices play an important role in depth perception. Moreover, in the absence of differences in the early visual cortex, the decrease is inconsistent with transsynaptic degeneration propagating from the degenerated retinal axons

Morphometric analyses of the visual pathways in macular degeneration

Introduction. Macular degeneration (MD) causes central visual field loss. When field defects occur in both eyes and overlap, parts of the visual pathways are no longer stimulated. Previous reports have shown that this affects the grey matter of the primary visual cortex, but possible effects on the preceding visual pathway structures have not been fully established. Method. In this multicentre study, we used high-resolution anatomical magnetic resonance imaging and voxel-based morphometry to investigate the visual pathway structures up to the primary visual cortex of patients with age-related macular degeneration (AMD) and juvenile macular degeneration (JMD). Results. Compared to age-matched healthy controls, in patients with JMD we found volumetric reductions in the optic nerves, the chiasm, the lateral geniculate bodies, the optic radiations and the visual cortex. In patients with AMD we found volumetric reductions in the lateral geniculate bodies, the optic radiations and the visual cortex. An unexpected finding was that AMD, but not JMD, was associated with a reduction in frontal white matter volume. Conclusion. MD is associated with degeneration of structures along the visual pathways. A reduction in frontal white matter volume only present in the AMD patients may constitute a neural correlate of previously reported association between AMD and mild cognitive impairment. Keywords: macular degeneration - visual pathway - visual field - voxel-based morphometryComment: appears in Cortex (2013

White matter alterations in glaucoma and monocular blindness differ outside the visual system

The degree to which glaucoma has effects in the brain beyond the eye and the visual pathways is unclear. To clarify this, we investigated white matter microstructure (WMM) in 37 tracts of patients with glaucoma, monocular blindness, and controls. We used brainlife.io for reproducibility. White matter tracts were subdivided into seven categories ranging from those primarily involved in vision (the visual white matter) to those primarily involved in cognition and motor control. In the vision tracts, WMM was decreased as measured by fractional anisotropy in both glaucoma and monocular blind subjects compared to controls, suggesting neurodegeneration due to reduced sensory inputs. A test-retest approach was used to validate these results. The pattern of results was different in monocular blind subjects, where WMM properties increased outside the visual white matter as compared to controls. This pattern of results suggests that whereas in the monocular blind loss of visual input might promote white matter reorganization outside of the early visual system, such reorganization might be reduced or absent in glaucoma. The results provide indirect evidence that in glaucoma unknown factors might limit the reorganization as seen in other patient groups following visual loss

Surface-Based Analyses of Anatomical Properties of the Visual Cortex in Macular Degeneration

INTRODUCTION: Macular degeneration (MD) can cause a central visual field defect. In a previous study, we found volumetric reductions along the entire visual pathways of MD patients, possibly indicating degeneration of inactive neuronal tissue. This may have important implications. In particular, new therapeutic strategies to restore retinal function rely on intact visual pathways and cortex to reestablish visual function. Here we reanalyze the data of our previous study using surface-based morphometry (SBM) rather than voxel-based morphometry (VBM). This can help determine the robustness of the findings and will lead to a better understanding of the nature of neuroanatomical changes associated with MD. METHODS: The metrics of interest were acquired by performing SBM analysis on T1-weighted MRI data acquired from 113 subjects: patients with juvenile MD (JMD; n = 34), patients with age-related MD (AMD; n = 24) and healthy age-matched controls (HC; n = 55). RESULTS: Relative to age-matched controls, JMD patients showed a thinner cortex, a smaller cortical surface area and a lower grey matter volume in V1 and V2, while AMD patients showed thinning of the cortex in V2. Neither patient group showed a significant difference in mean curvature of the visual cortex. DISCUSSION: The thinner cortex, smaller surface area and lower grey matter volume in the visual cortex of JMD patients are consistent with our previous results showing a volumetric reduction in their visual cortex. Finding comparable results using two rather different analysis techniques suggests the presence of marked cortical degeneration in the JMD patients. In the AMD patients, we found a thinner cortex in V2 but not in V1. In contrast to our previous VBM analysis, SBM revealed no volumetric reductions of the visual cortex. This suggests that the cortical changes in AMD patients are relatively subtle, as they apparently can be missed by one of the methods

Morphometric analyses of the visual pathway in macular degeneration

Introduction: Central retinal lesions caused by macular degeneration result in depriving visual pathway structures of activity. This, in turn, could result in anatomical and functional changes of visual pathway structures. If such changes in the visual pathway structures remain permanent they could limit the success of future treatments that aim to restore retinal function, such as retinal implants and a stem-cell-derived retinal epithelium. In a multi-centre study, we asked the question whether macular degeneration, both juvenile macular degeneration (JMD) and age-related macular degeneration (AMD), is associated with volumetric changes of visual pathway structures, and if there is any relationship between visual function, such as visual acuity, and the volume of the visual pathway structures. Methods: High-resolution anatomical magnetic resonance imaging (MRI) data were obtained in participants with either JMD or AMD, as well as in age-matched healthy controls. We separated the visual pathway structures from the rest of the brain in T1 MRI volumes. Voxel-based morphometry (VBM) was used to evaluate statistically the volumetric differences between patients and age-matched controls. Results: Comparison of patients with controls shows a lower volume of the LGB in both patient groups. Comparison of white matter between the groups revealed volumetric reductions in the optic radiations of the patients. Also in the grey matter in the visual cortex, the volume is reduced in patients compared to controls. All effects were visible in both the JMD and the AMD group. Results were most clear in the JMD group. Discussion and conclusion: Our main finding is that there is volumetric loss in the LGB and in the white matter of the visual pathways in macular degeneration. Our findings that there is also a decrease in grey matter in the visual cortex, complements previous studies. Further investigation of changes in the visual pathway structures in macular degeneration is needed, for a better understanding of the structure-function relationship in macular degeneration.

Structural brain MRI studies in eye diseases:are they clinically relevant? A review of current findings

Many eye diseases reduce visual acuity or are associated with visual field defects. Because of the well-defined retinotopic organization of the connections of the visual pathways, this may affect specific parts of the visual pathways and cortex, as a result of either deprivation or transsynaptic degeneration. For this reason, over the past several years, numerous structural magnetic resonance imaging(MRI) studies have examined the association of eye diseases with pathway and brain changes. Here, we review structural MRI studies performed in human patients with the eye diseases albinism, amblyopia, hereditary retinal dystrophies, age-related macular degeneration (AMD) and glaucoma. We focus on two main questions. First, what have these studies revealed? Second, what is the potential clinical relevance of their findings? We find that all the aforementioned eye diseases are indeed associated with structural changes in the visual pathways and brain. As such changes have been described in very different eye diseases, in our view the most parsimonious explanation is that these are caused by the loss of visual input and the subsequent deprivation of the visual pathways and brain regions, rather than by transsynaptic degeneration. Moreover, and of clinical relevance, for some of the diseases -in particular glaucoma and AMD -present results are compatible with the view that the eye disease is part of a more general neurological or neurodegenerative disorder that also affects the brain. Finally, establishing structural changes of the visual pathways has been relevant in the context of new therapeutic strategies to restore retinal function: it implies that restoring retinal function may not suffice to also effectively restore vision. Future structural MRI studies can contribute to (i) further establish relationships between ocular and neurological neurodegenerative disorders, (ii) investigate whether brain degeneration in eye diseases is reversible, (iii) evaluate the use of neuroprotective medication in ocular disease, (iv) determine optimal timing for retinal implant insertion and (v) establish structural MRI examination as a diagnostic tool in ophthalmology