Abstract
We hypothesized that assessment of brain connectivity may shed light on the underpinnings of ocular hypertension (OHT), characterized by raised intraocular pressure (IOP) and no typical glaucomatous findings. OHT carries a risk for future glaucoma development, thus representing a model of presymptomatic condition. In previous studies on glaucoma, we showed altered brain connectivity since the early stage and in case of normal IOP. In this pilot study, we used a multimodal MRI approach by modeling voxelwise measures of gray matter volume, anatomical connectivity along white matter(WM) tracts, and large-scale functional connectivity in OHT subjects (n = 18, age: 58.3 ± 9.8 years) and demographically matched normal controls (n = 29). While OHT brain had no structural alterations, it showed significantly decreased functional connectivity in key cognitive networks [default mode network, frontoparietal working memory network (WMN), ventral attention network (VAN), and salience network (SN)] and altered long-range functional connectivity, which was decreased between default mode and SNs and increased between primary and secondary visual networks (VN). Overall, such findings seem to delineate a complex neuroplasticity in the OHT brain, where decreased functional connectivity in non-visual networks may reflect a type of temporarily downregulated functional reserve while increased functional connectivity between VN may be viewed as a very early attempt of adaptive functional reorganization of the visual system.
Highlights
The term ocular hypertension (OHT) is traditionally applied to a condition with raised intraocular pressure (IOP) (≥22 mmHg or >2 standard deviations above the mean value) without typical glaucomatous visual field deficits, alterations of the optic nerve head, and retinal ganglion cell degeneration.The prevalence estimates for OHT in the general population range from 4.5 to 9.4% for people aged >40 years, with an increasing trend with aging (Burr et al, 2012)
No significant differences were found between OHT and NC in terms of age (p = 0.85), sex (p = 0.9), and grade of white matter (WM) hyperintensities (p = 0.44; grade 0: 61% vs. 72.4%; grade 1: 39.9% vs. 24.1%; grade 2: 0% vs. 3.5%; no grade 3 in either groups) (Table 1)
The traditional view of glaucoma as pure ocular condition with damage to optic nerve head and retinal ganglion cells has been recently challenged and expanded by various advanced magnetic resonance imaging (MRI) studies, which demonstrated the presence of a diffuse neurodegeneration process across the brain, involving nonvisual system (Nuzzi et al, 2018)
Summary
The term ocular hypertension (OHT) is traditionally applied to a condition with raised intraocular pressure (IOP) (≥22 mmHg or >2 standard deviations above the mean value) without typical glaucomatous visual field deficits, alterations of the optic nerve head, and retinal ganglion cell degeneration.The prevalence estimates for OHT in the general population range from 4.5 to 9.4% for people aged >40 years, with an increasing trend with aging (Burr et al, 2012). The term ocular hypertension (OHT) is traditionally applied to a condition with raised intraocular pressure (IOP) (≥22 mmHg or >2 standard deviations above the mean value) without typical glaucomatous visual field deficits, alterations of the optic nerve head, and retinal ganglion cell degeneration. Data from longitudinal studies indicate that development of primary open angle glaucoma (POAG) within 5 years occurs in around 10% of people with untreated OHT and in 5% of those on medication (Weinreb et al, 2014). Because of this risk, OHT may represent a model of presymptomatic condition. IOP reduction is still the main treatment option available
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