Early changes of brain connectivity in primary open angle glaucoma

Abstract

Our aim was to assess in primary open angle glaucoma (POAG), a major cause of irreversible blindness worldwide, whether diffuse brain changes recently shown in advanced stage can be detected since the early stage. We used multimodal magnetic resonance imaging (MRI) in 57 patients with the three POAG stages and in 29 age-matched normal controls (NC). Voxelwise statistics was performed with nonparametric permutation testing. Compared with NC, disrupted anatomical connectivity (AC) was found in the whole POAG group along the visual pathway and in nonvisual white matter tracts (P < 0.001). Moreover, POAG patients showed decreased functional connectivity (FC) in the visual (P = 0.004) and working memory (P < 0.001) networks whereas an increase occurred in the default mode (P = 0.002) and subcortical (P < 0.001) networks. Altered AC and FC were already present in early POAG (n = 14) in both visual and nonvisual systems (P ≤ 0.01). Only severe POAG (n = 30) showed gray matter atrophy and this mapped on visual cortex (P < 0.001) and hippocampus (P < 0.001). Increasing POAG stage was associated with worsening AC in both visual and nonvisual pathway (P < 0.001), progressive atrophy in the hippocampus and frontal cortex (P < 0.003). Most of the structural and functional alterations within and outside the visual system showed correlation (P < 0.001 to 0.02) with computerized visual field and retinal nerve fiber layer thickness. In conclusion, the complex pathogenesis of POAG includes widespread damage of AC and altered FC within and beyond the visual system since the early disease stage. The association of brain MRI changes with measures of visual severity emphasizes the clinical relevance of our findings. Hum Brain Mapp 37:4581-4596, 2016. © 2016 Wiley Periodicals, Inc.

Optic Radiations Microstructural Changes in Glaucoma and Association With Severity: A Study Using 3Tesla-Magnetic Resonance Diffusion Tensor Imaging

“…Finally, functional MRI may offer new insights into the brain modifications associated with glaucoma, as suggested by two recent studies, showing functional modifications of the visual cortex at the earliest stages of the disease. 47,48 In conclusion, we confirmed microstructural changes of optic radiations in glaucoma and its association with glaucoma severity. In accordance with several other studies, DTI appears as an objective measurement for evaluating alterations of the visual pathways in glaucoma and provides new insight in the pathophysiological process of glaucoma.…”

Diffuse brain damage in normal tension glaucoma

“…In fact, NTG cases represent about 25–32% of overall POAG cases, both in the Beaver Dam study in Wisconsin, USA [Klein et al, ] and in the Egna Neumarkt study in Alto Adige, Italy [Bonomi et al, ] whereas NTG prevalence is three to four times higher than HTG in Japan [Shiose et al, ]. In POAG with raised IOP, we and others have previously demonstrated through multimodal brain MRI widespread damage of diffusion tensor imaging (DTI)‐derived anatomical connectivity (AC), gray matter (GM) atrophy and/or altered resting state functional connectivity (FC) that can go beyond the visual system, even since the early disease stage [Dai et al, ; Frezzotti et al, ; Jiang et al, ; Wang et al, ; Zikou et al, ].…”

Disrupted Eye Movements in Preperimetric Primary Open-Angle Glaucoma

“…3 Recent multimodal, cerebral MRI and diffusion tensor imaging studies have shown diffuse structural and functional changes in the brains of patients with different stages of glaucoma. 10,11 These changes affected visual and nonvisual structures in the brain. Beyond atrophy of the visual cortex, these studies disclosed atrophy of scattered, distant gray matter regions such as the frontoparietal cortex, hippocampi, and cerebellar cortex, and decreased functional connectivity in visual, working memory and dorsal attention networks.…”

“…The same study in glaucoma disclosed altered integrity of the superior longitudinal fascicle, resulting in decreased fractional anisotropy. 11 This fascicle is involved in providing information regarding perception of visual space to the prefrontal cortex, which in turn is responsible for the planning phase of an antisaccade. 52 Furthermore, the white matter of the precuneus showed abnormalities even in earlystage POAG.…”

“…52 Furthermore, the white matter of the precuneus showed abnormalities even in earlystage POAG. 11 This parietal brain structure has major subcortical connections in brainstem structures with strong oculomotor characteristics, such as the pretectal area, the SC, and the nucleus reticularis tegmenti pontis. [53][54][55] Given the developmental, physiological, and anatomical features that the retina shares with the brain, 56 it is not surprising that functional changes affecting the retina could also translate into cerebral dysfunctions and vice versa.…”