Neurodegeneration beyond the primary visual pathways in a population with a high incidence of normal‐pressure glaucoma

Abstract

Citation information: Boucard CC, Hanekamp S, C ´ urč ic´-ic´ic´-Blake B, Ida M, Yoshida M & Cornelissen FW. Neurodegeneration beyond the primary visual pathways in a population with a high incidence of normal-pressure glaucoma. Abstract Purpose: Glaucoma is the most common age-related neurodegenerative eye disease in western society. It is an insidious disease that, when untreated or detected too late, leads inevitably to blindness. An outstanding issue is whether glaucoma should be considered exclusively an eye disease or also a brain disease. To further examine it, we used Diffusion Tensor Imaging (DTI) to study white matter integrity in a Japanese glaucoma population. This population has a very high incidence of normal-pressure glaucoma, in which optic nerve damage occurs in the absence of the elevated eye pressure that characterises the more common form of glaucoma. Methods: We performed DTI in 30 participants with normal-pressure glaucoma and 21 age-matched healthy controls. We used voxel-wise tract-based spatial statistics to compare fractional anisotropy and mean diffusivity of the white matter of the brain between patients and control group. Whole-brain and region of interest-based analyses served to find associations between diffusion indices and clinical measures of glaucomatous damage. Results: Fractional Anisotropy was significantly lower in glaucoma patients in a cluster in the right occipital lobe (p < 0.05; family-wise error-corrected) comprising fibres of both the optic radiation and the forceps major. Additional analysis confirmed bilateral involvement of the optic radiations and forceps major and additionally revealed damage to the corpus callosum and parietal lobe (p < 0.09; family-wise error-corrected). The region of interest-based analysis revealed a positive association between Fractional Anisotropy of the optic radiation and optic nerve damage. Conclusions: In this specific population, glaucoma is associated with lower Fractional Anisotropy in the optic radiations, forceps major and corpus callosum. We interpret these reductions as evidence for white matter degeneration in these loci. In particular, the degeneration of the corpus callosum suggests the presence of neurodegeneration of the brain beyond what can be explained on the basis of propagated retinal and pre-geniculate damage. We discuss how this finding links to the emerging view that a brain component that is independent from the eye damage plays a role in the aetiology of glaucoma.

Altered white matter structure in the visual system following early monocular enucleation

“…The smaller FA value contralateral to the enucleated eye may be explained by the relatively smaller LGN and optic tract volumes previously demonstrated contralateral to the enucleated eye in this specific ME sample [Kelly et al, ]. Previous studies of long‐term visual deprivation have commonly interpreted a reduction in FA as the consequence of transneuronal degeneration or axonal immaturity [Boucard et al, ; Shu et al, ]. Transneuronal degeneration could certainly account for the observed change in FA if, for example, the smaller LGN contralateral to the enucleated eye supports fewer efferent fibers extending to V1, or if the reduction in visual input results in disuse atrophy.…”

“…The relatively weaker physiological input to the hemisphere contralateral to the nondominant eye [Toosy et al, ], or in this case, the enucleated eye, is likely compounded by changes to the visual pathway structures (e.g., optic tract and LGN) [Kelly et al, ] in the same hemisphere resulting in further reduced V1 activity [Barb et al, ]. Reduced functional activity can disrupt normal corticothalamic feedback [Cudeiro and Sillito, ], causing axonal degeneration or immaturity [Boucard et al, ; Shu et al, ], and likely results in the disorganization of the V1‐LGN tracts. Similarly, the structural changes in V1 of these ME participants may also play a role.…”

Diffuse brain damage in normal tension glaucoma

“…In a recent DTI study on NTG patients from Japan, where the disease has a high prevalence, using a similar analysis (TBSS) but a different statistical approach, decreased FA was found compared to NC in the occipital WM comprising OR and F maj but also in nonvisual areas such as CC and parietal lobe [Boucard et al, ]. Because our study on a relatively small population has an exploratory nature, we used a less conservative threshold compared with the above study.…”

“…An MRI study on the anterior visual pathway of NTG showed reduced volumetry and altered DTI measures, which correlated with RNFL thickness and VF measures [Zhang et al, ]. A more recent DTI study in NTG patients from Japan, where the disease has a high prevalence, found decreased fractional anisotropy (FA) compared with normal controls (NC) in the occipital WM comprising optic radiations (OR) and forceps major ( F maj ) but also in nonvisual areas such as corpus callosum (CC) and parietal lobe [Boucard et al, ].…”

Visualisation of the visual system

“…The special issue also emphasised fundamental research questions that can be addressed with imaging. These included diurnal changes in ocular tissues, the use of imaging to understand and diagnose retinal disease and the extent to which the brain changes its structure and function in individuals with macular degeneration or glaucoma . In addition, contemporary themes in vision science imaging research were identified by two invited review papers featured within the special issue.…”