Abstract
Purpose:
A number of recent studies, by using quantitative MRI, have showed that patients with primary open-angle glaucoma (POAG) can have significant damage in brain areas of the visual system. However, it is less clear whether brain changes are limited only to the visual system. We have recently demonstrated on a small group of patients with advanced POAG the presence of structural and functional brain changes beyond visual system (Frezzotti P, Giorgio A, et al. PLoS ONE 2014 9(8): e105931). To expand our preliminary observation, we examined brain structural changes in a large group of patients with different POAG stages.
Methods:
We performed in 95 patients with POAG a complete visual assessement, conventional MRI and diffusion tensor imaging. Data were compared with those of age-matched normal controls (NC, n=30). We used FSL tools such as tract-based spatial statistics for evaluation of microstructural integrity of white matter (WM) tracts, a voxel based morphometry-style analysis of regional grey matter (GM) volume and FIRST for the assessment of deep GM structures. Nonparametric permutation testing across the whole brain using threshold-free cluster enhancement was used for all voxelwise analyses (p<0.005 uncorrected, k≥20 voxels). ANOVA corrected for age and sex was used for between-group comparison of deep GM structures.
Results:
Altered microstructural integrity (decreased fractional anisotropy [0.34±0.02 vs 0.40±0.02, p<0.001] or increased axial [1.28±0.03 vs 1.20±0.02 x 10-3 mm2/s, p<0.001] and radial [0.80±0.07 vs 0.52±0.02 x 10-3 mm2/s, p<0.001] diffusivity) of WM tracts was found not only along the visual pathways but also in nonvisual WM tracts<br /> Moreover, POAG patients showed GM atrophy in comparison with NC in medial visual cortex (lingual gyrus) and in the cerebellar cortex (10.34±0.45 vs 12.82±0.73 cm3, p<0.001). As for the deep GM, POAG patients showed significant volume reduction in the hippocampi (4.58±0.60 cm3 vs 5.05±0.64 cm3, p=0.03, on the right; 4.63 ±0.53 cm3 vs 5.05±0.56 cm3; p=0.02 on the left), and a marginal significance for the left accumbens (p-0.05) and left thalamus (p=0.07).
Conclusions:
Overall, these results suggest that in patients with POAG structural changes in the WM and GM occur well beyond the visual system. These findings provide new evidence that POAG can be considered a vision disorder belonging to the group of neurodegenerative conditions.