Abstract
Purpose :
In order to test the hypothesis that in primary open angle glaucoma a spreading of neurodegeneration occurs through the brain, this study investigates the correlation of glaucoma severity indicators with parameters of axonal and myelin integrity of the whole-brain
Methods :
We performed multimodal MRI and subsequent whole-brain explorative voxelwise analyses in 17 primary open angle glaucoma /High Pressure Glaucoma (POAG/HPG) patients, 17 primary open angle glaucoma/Normal Pressure glaucoma (POAG/NPG), and 29 age-matched normal controls (NC). POAG patients were classified according to the Hodapp/Bascom Palmer classification. We used multimodal magnetic resonance imaging (MRI) in 34 patients with the three POAG stages and in 29 age-matched normal controls (NC). Voxelwise statistics was performed with nonparametric permutation testing
Results :
Compared with NC, disrupted anatomical connectivity (AC) was found in the whole POAG group (HPG and NPG) 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=20) in both visual and nonvisual systems (P<0.01). Only severe POAG (n=10) 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 NPG patients changes seem to be less compared to those seen in patients with HPG.
Conclusions :
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. In NPG patients this lower impairment in the brain is anyway significant and less dependent on intraocular pressure
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.