MRI and Clinical Biomarkers Overlap between Glaucoma and Alzheimer's Disease.

Glaucoma is the leading cause of blindness worldwide. It is classically associated with structural and functional changes in the optic nerve head and retinal nerve fiber layer, but the damage is not limited to the eye. The involvement of the central visual pathways and disruption of brain network organization have been reported using advanced neuroimaging techniques. The brain structural changes at the level of the areas implied in processing visual information could justify the discrepancy between signs and symptoms and underlie the analogy of this disease with neurodegenerative dementias, such as Alzheimer's disease, and with the complex group of pathologies commonly referred to as "disconnection syndromes." This review aims to summarize the current state of the art on the use of advanced neuroimaging techniques in glaucoma and Alzheimer's disease, highlighting the emerging biomarkers shared by both diseases.

Biochemical-molecular-genetic biomarkers in the tear film, aqueous humor, and blood of primary open-angle glaucoma patients.

Introduction: Glaucoma is a chronic neurodegenerative disease, which is the leading cause of irreversible blindness worldwide. As a response to high intraocular pressure, the clinical and molecular glaucoma biomarkers indicate the biological state of the visual system. Classical and uncovering novel biomarkers of glaucoma development and progression, follow-up, and monitoring the response to treatment are key objectives to improve vision outcomes. While the glaucoma imaging field has successfully validated biomarkers of disease progression, there is still a considerable need for developing new biomarkers of early glaucoma, that is, at the preclinical and initial glaucoma stages. Outstanding clinical trials and animal-model study designs, innovative technology, and analytical approaches in bioinformatics are essential tools to successfully uncover novel glaucoma biomarkers with a high potential for translation into clinical practice. Methods: To better understand the clinical and biochemical-molecular-genetic glaucoma pathogenesis, we conducted an analytical, observational, and case-comparative/control study in 358 primary open-angle glaucoma (POAG) patients and 226 comparative-control individuals (CG) to collect tears, aqueous humor, and blood samples to be processed for identifying POAG biomarkers by exploring several biological pathways, such as inflammation, neurotransmitter/neurotrophin alteration, oxidative stress, gene expression, miRNAs fingerprint and its biological targets, and vascular endothelial dysfunction, Statistics were done by using the IBM SPSS 25.0 program. Differences were considered statistically significant when p ≤ 0.05. Results: Mean age of the POAG patients was 70.03 ± 9.23 years, and 70.62 ± 7.89 years in the CG. Malondialdehyde (MDA), nitric oxide (NO), interleuquin (IL)-6, endothelin-1 (ET-1), and 5 hydroxyindolacetic acid (5-HIAA), displayed significantly higher levels in the POAG patients vs. the CG (p < 0.001). Total antioxidant capacity (TAC), brain derived neurotrophic factor (BDNF), 5-hydroxy tryptamine (5-HT), solute carrier family 23-nucleobase transporters-member 2 (SLC23A2) gene, and the glutathione peroxidase 4 (GPX4) gene, showed significantly lower levelsin the POAG patients than in the CG (p < 0.001). The miRNAs that differentially expressed in tear samples of the POAG patients respect to the CG were the hsa miR-26b-5p (involved in cell proliferation and apoptosis), hsa miR-152-3p (regulator of cell proliferation, and extracellular matrix expression), hsa miR-30e-5p (regulator of autophagy and apoptosis), and hsa miR-151a-3p (regulator of myoblast proliferation). Discussion: We are incredibly enthusiastic gathering as much information as possible on POAG biomarkers to learn how the above information can be used to better steer the diagnosis and therapy of glaucoma to prevent blindness in the predictable future. In fact, we may suggest that the design and development of blended biomarkers is a more appropriate solution in ophthalmological practice for early diagnosis and to predict therapeutic response in the POAG patients.

Imaging biomarkers for Alzheimer's disease and glaucoma: Current and future practices.

Glaucoma is a leading cause of blindness worldwide. Although intraocular pressure is the main risk factor for glaucoma, several intraocular pressure independent factors have been associated with the risk of developing the disease and its progression. The diagnosis of glaucoma relies on clinical features of the optic nerve, visual field test, and optical coherence tomography. However, the multidisciplinary aspect of the disease suggests that other biomarkers may be useful for the diagnosis, thus underling the importance of novel imaging techniques supporting clinicians. This review analyzes the common pathogenic mechanisms between glaucoma and Alzheimer's disease and the possible novel approaches for diagnosis and follow up.

Optical coherence tomography angiography in the multimodal assessment of the retinal posterior pole in autosomal dominant optic atrophy.

PURPOSE: To assess retinal vascular involvement in patients with autosomal dominant optic atrophy (ADOA) genetically confirmed by the presence of the OPA1 (Optic Atrophy 1) gene mutation using a multimodal protocol of investigation of retinal posterior pole. METHODS: In this cross-sectional, case-control, observational study, both eyes of 13 patients with a genetic diagnosis of ADOA were compared with both eyes of 13 healthy controls (HCs). All subjects underwent full ophthalmological examination, spectral domain-optical coherence tomography (SD-OCT), fundus perimetry (FP) and OCT angiography (OCTA). RESULTS: Vessel density (VD) of the superficial and deep macular vascular plexi and of the radial peripapillary capillary plexus were significantly decreased (p ≤ 0.001) in ADOA patients compared with HCs. The area under the receiver operating characteristics analysis also revealed high values of sensitivity and specificity of OCTA parameters in distinguish between patients and HCs. A strong correlation (Pearson Coefficient, r = 0.91) emerged between OCTA VD of the superficial retinal plexus and the average Ganglion Cell Layer (GCL) thickness as measured by SD-OCT; a slightly lower correlation (Pearson Coefficient, r = 0.89) was also found between VD of the deep plexus and the average GCL thickness of the same eyes in patients with ADOA. The correlation among values of differential light sensitivity (DLS) measured by FP with VD and GCL thickness parameters was also investigated. The correlation analysis among DLS and the VD parameters showed from low-to-moderate correlation (ranging from r = 0.29 for the deep fovea VD to r = 0.59 for the deep whole image VD). The correlation coefficient between the mean DLS and the average thickness of GCL was more significant (Pearson Coefficient, r = 0.75). A significant correlation emerged also between the VD and the visual acuity, in terms of LogMAR BCVA (best-corrected visual acuity), especially for the VD of the deep capillary plexus (Pearson Coefficient for the Deep whole Image VD and LogMAR BCVA r = -0.75; for the Deep parafovea VD and LogMAR BCVA r = -0.78). CONCLUSION: Retinal microvascular assessment by OCTA angiography can provide relevant clinical information on retinal involvement in ADOA patients. In patients with genetically confirmed OPA1-related ADOA, there is a decrease in retinal vessel density associated with GCL thinning and DLS reduction.

Combined use of coenzyme Q10 and citicoline: A new possibility for patients with glaucoma.

Glaucoma is the leading cause of irreversible blindness worldwide. Several risk factors have been involved in the pathogenesis of the disease. By now, the main treatable risk factor is elevated intraocular pressure. Nevertheless, some patients, whose intraocular pressure is considered in the target level, still experience a progression of the disease. Glaucoma is a form of multifactorial ocular neurodegeneration with complex etiology, pathogenesis, and pathology. New evidence strongly suggests brain involvement in all aspects of this disease. This hypothesis and the need to prevent glaucomatous progression led to a growing interest in the pharmacological research of new neuroprotective, non-IOP-lowering, agents. The aim of this paper is to report evidence of the usefulness of Coenzyme Q10 and Citicoline, eventually combined, in the prevention of glaucomatous neurodegeneration.

Complex Rearrangement of the Entire Retinal Posterior Pole in Patients with Relapsing Remitting Multiple Sclerosis.

There are consolidated data about multiple sclerosis (MS)-dependent retinal neurodegeneration occurring in the optic disk and the macula, although it is unclear whether other retinal regions are affected. Our objective is to evaluate, for the first time, the involvement of the entire retinal posterior pole in patients diagnosed with relapsing remitting multiple sclerosis (RRMS) unaffected by optic neuritis using Spectral Domain-Optical Coherence Tomography (SD-OCT). The study protocol was approved by Tor Vergata Hospital Institutional Ethics Committee (Approval number 107/16), and conforms to the tenets of the Declaration of Helsinki. After a comprehensive neurological and ophthalmological examination, 53 untreated RRMS patients (aged 37.4 ± 10) and 53 matched controls (aged 36.11 ± 12.94) were enrolled. In addition, each patient underwent an examination of the posterior pole using the SD-OCT built-in Spectralis posterior pole scanning protocol. After segmentation, the mean thickness, as well as the thickness of the 64 single regions of interest, were calculated for each retinal layer. No statistically significant difference in terms of average retinal thickness was found between the groups. However, MS patients showed both a significantly thinner ganglion cell layer (p < 0.001), and, although not statistically significant, a thinner inner nuclear layer (p = 0.072) and retinal nerve fiber layer (p = 0.074). In contrast, the retinal pigment epithelium (p = 0.014) and photoreceptor layers p < 0.001) resulted significantly thicker in these patients. Interestingly, the analysis of the region of interest showed that neurodegeneration was non-homogeneously distributed across each layer. This is the first report that suggests a complex rearrangement that affects, layer by layer, the entire retinal posterior pole of RRMS retinas in response to the underlying neurotoxic insult.

CannabinEYEds: The Endocannabinoid System as a Regulator of the Ocular Surface Nociception, Inflammatory Response, Neovascularization and Wound Healing.

The endocannabinoid system (ECS) is a complex regulatory system, highly conserved among vertebrates. It has been widely described in nearly all human tissues. In the conjunctiva and cornea, the ECS is believed to play a pivotal role in the modulation of the local inflammatory state as well as in the regulation of tissue repair and fibrosis, neo-angiogenesis and pain perception. This review aims to summarize all the available data on ECS expression and its function in ocular surface structures to provide a specific insight concerning its modulation in dry eye disease, and to propose directions for future research.

Reorganization of the structural connectome in primary open angle Glaucoma.

Primary open angle Glaucoma (POAG) is one of the most common causes of permanent blindness in the world. Recent studies have suggested the hypothesis that POAG is also a central nervous system disorder which may result in additional (i.e., extra-ocular) involvement. The aim of this study is to assess possible structural, whole-brain connectivity alterations in POAG patients. We evaluated 23 POAG patients and 15 healthy controls by combining multi-shell diffusion weighted imaging, multi-shell, multi-tissue probabilistic tractography, graph theoretical measures and a recently designed 'disruption index', which evaluates the global reorganization of brain networks. We also studied the associations between the whole-brain structural connectivity measures and indices of visual acuity including the field index (VFI) and two Optical Coherence Tomography (OCT) parameters, namely the Macula Ganglion Cell Layer (MaculaGCL) and Retinal Nerve Fiber Layer (RNFL) thicknesses. We found both global and local structural connectivity differences between POAG patients and controls, which extended well beyond the primary visual pathway and were localized in the left calcarine gyrus (clustering coefficient p = 0.036), left lateral occipital cortex (clustering coefficient p = 0.017, local efficiency p = 0.035), right lingual gyrus (clustering coefficient p = 0.009), and right paracentral lobule (clustering coefficient p = 0.009, local efficiency p = 0.018). Group-wise (clustering coefficient, p = 6.59∙10-7 and local efficiency p = 6.23·10-8) and subject-wise disruption indices (clustering coefficient, p = 0.018 and local efficiency, p = 0.01) also differed between POAG patients and controls. In addition, we found negative associations between RNFL thickness and local measures (clustering coefficient, local efficiency and strength) in the right amygdala (local efficiency p = 0.008, local strength p = 0.016), right inferior temporal gyrus (clustering coefficient p = 0.036, local efficiency p = 0.042), and right temporal pole (local strength p = 0.008). Overall, we show, in patients with POAG, a whole-brain structural reorganization that spans across a variety of brain regions involved in visual processing, motor control, and emotional/cognitive functions. We also identified a pattern of brain structural changes in relation to POAG clinical severity. Taken together, our findings support the hypothesis that the reduction in visual acuity from POAG can be driven by a combination of local (i.e., in the eye) and more extended (i.e., brain) effects.

Diffusional Kurtosis Imaging of White Matter Degeneration in Glaucoma.

Glaucoma is an optic neuropathy characterized by death of retinal ganglion cells and loss of their axons, progressively leading to blindness. Recently, glaucoma has been conceptualized as a more diffuse neurodegenerative disorder involving the optic nerve and also the entire brain. Consistently, previous studies have used a variety of magnetic resonance imaging (MRI) techniques and described widespread changes in the grey and white matter of patients. Diffusion kurtosis imaging (DKI) provides additional information as compared with diffusion tensor imaging (DTI), and consistently provides higher sensitivity to early microstructural white matter modification. In this study, we employ DKI to evaluate differences among healthy controls and a mixed population of primary open angle glaucoma patients ranging from stage I to V according to Hodapp-Parrish-Anderson visual field impairment classification. To this end, a cohort of patients affected by primary open angle glaucoma (n = 23) and a group of healthy volunteers (n = 15) were prospectively enrolled and underwent an ophthalmological evaluation followed by magnetic resonance imaging (MRI) using a 3T MR scanner. After estimating both DTI indices, whole-brain, voxel-wise statistical comparisons were performed in white matter using Tract-Based Spatial Statistics (TBSS). We found widespread differences in several white matter tracts in patients with glaucoma relative to controls in several metrics (mean kurtosis, kurtosis anisotropy, radial kurtosis, and fractional anisotropy) which involved localization well beyond the visual pathways, and involved cognitive, motor, face recognition, and orientation functions amongst others. Our findings lend further support to a causal brain involvement in glaucoma and offer alternative explanations for a number of multidomain impairments often observed in glaucoma patients.

Links between obstructive sleep apnea and glaucoma neurodegeneration.

In the last few years, the possible link between obstructive sleep apnea (OSAS) and glaucoma, has attracted the interest of many scientists, especially in those forms of primary open angle glaucoma (POAG) and normal tension glaucoma (NTG), in which a progression of the disease occurs, even though intraocular pressure (IOP) is in the range of normality. The increased prevalence of POAG or NTG in patients affected by OSAS, and vice versa, has stimulated interest in the pathogenetic mechanisms that could trigger these two diseases. Hypoxia generated by apnea/hypopnea cycles has been identified as the main cause of many changes in the vascular and neurological systems, which alter the functioning not only of the optic nerve, but also of the whole organism. However, many other factors could be involved, like mechanical factors, obesity, hormonal imbalance and other sleep disorders. Furthermore, the demonstration of typical glaucomatous or glaucoma-like changes in the anatomy or function of the optic nerve and retinal nerve fiber layer by sensitive specific and diagnostic methods, such as perimetry, optical coherence tomography (OCT), optical coherence tomography angiography (OCTA) and electrophysiological exams keeps interest high for this field of study. For this reason, further investigations, hopefully a source of stronger scientific evidences, are needed.

Brain networks reorganization and functional disability in glaucoma.

Glaucoma is an optic neuropathy characterized by progressive loss of retinal ganglion cells with associated structural and functional changes of the optic nerve head and retinal nerve fiber layer. However, recent studies employing advanced neuroimaging techniques confirmed that glaucomatous damage is not limited to the eye but extends to the brain, affecting it also beyond the central visual pathways and disrupting brain network organization. We therefore posit that, while visual field changes play an important role in glaucoma-induced disability, central nervous pathways and mechanisms may play an important role in sustaining functional and daily living disability caused by the disease. Here we to summarize the current state of the art on the involvement of central brain circuits and possibly related disabilities in patients with glaucoma.

Evaluation of putative differences in vessel density and flow area in normal tension and high-pressure glaucoma using OCT-angiography.

PURPOSE: To evaluate the putative differences in terms of vessel density and flow area between control (CTRL), high-pressure glaucoma (HPG) and normal tension glaucoma (NTG) subjects at macular and peripapillary level. To assess the correlation between Visual Field Index (VFI), the stage of glaucoma, and optical coherence tomography angiography (OCT-A) parameters. MATERIAL AND METHODS: In this pilot, prospective study 46 eyes of 46 glaucomatous patients (19 NTG+27 HPG) and 25 control eyes (CTRL) of 25 subjects were recruited. All patients underwent a complete ophthalmologic examination and visual field testing. A 3×3mm volumetric macular scan (Angio Retina [3.0]) and a 4.5×4.5mm diameter peripapillary scan (Angio Disc [4.5]) were performed in the right eye using RTVue-XR Avanti (Optovue, Inc.) OCT-A. RESULTS: Groups were homogeneous for age (P=0.784) and gender (P=0.623). Among the evaluated optic nerve head (ONH) and macular OCT-A parameters, ONH whole image (P<0.001), inside disc (P=0.021), peripapillary (P<0.001), ONH flow area (P<0.026), macula whole image (P<0.001), fovea (P<0.001), parafovea (P<0.001) showed a significant difference when CTRL group was compared to HPG group at the post hoc test. Similarly, ONH whole image (P<0.001), inside disc (P=0.005), peripapillary (P<0.001), ONH flow area (P<0.026), macula whole image (P<0.001), FOVEA (P<0.001), parafovea (P<0.001) showed a significant difference were CTRL were compared to NTG group. On the contrary, no significant difference was found when NTG and HPG groups were compared. Age was not significantly correlated with any of the OCT-A parameters. The stage of the disease showed a high, significant, correlation with ONH whole image (r=-0.81; P<0.0001), inside disc (r=-0.42; P<0.0001), peripapillary (r=-0.81; P<0.0001), RNFL (r=-0.79; P<0.0001), macula whole image (r=0.56; P<0.0001), fovea (r=-0.78; P<0.0001) and parafovea (r=0.67; P<0.0001). On the contrary, VFI showed a high, significant, correlation with ONH whole image (r=0.77; P<0.0001), inside disc (r=0.39; P=0.0018), peripapillary (r=0.713; P<0.0001), RNFL (r=0.63; P<0.0001), macula whole image (r=-0.39; P=0.0007), fovea (r=0.60; P<0.0001) and parafovea (r=-0.52; P<0.0001). CONCLUSIONS: Our data support the usefulness of the OCT-A in the common clinical practice for diagnosis, staging, evaluating the progression of the disease as well as for better understanding of its pathogenic mechanisms.

Retinal and Choroidal Vasculature in Patients with Marfan Syndrome.

Purpose: To assess the retinal and choroidal vasculature in patients with genetically confirmed Marfan syndrome (MfS). Methods: This prospective, case-control, observational study included 48 eyes of 24 patients with a genetic diagnosis of MfS and compared them with 52 eyes of 26 healthy controls. Best-corrected visual acuity, choroidal and retinal thickness measured by spectral domain-optical coherence tomography, retinal and choroidal vasculature characterized by optical coherence tomography angiography, were collected. A genetic counseling was carried out. A transthoracic echocardiogram was performed to evaluate the dimension of the aortic root, the ascending aorta and the left ventricle function and dimensions. Results: A significant decrease in the superficial and deep retinal capillary plexi vessel density (VD) was evident, such as a decrease in the choriocapillaris plexus VD. In patients with MfS, a negative correlation between left ventricular diameter and the VD of the superficial and deep plexi was observed. Patients with MfS with greater posterior wall and interventricular septum dimensions had lower VD in both plexi (P < 0.05). Moreover, there was a negative correlation between the dimension of the ascending aorta and foveal choriocapillary VD. In patients with MfS, increasing diameter of the ascending aorta was associated with a lower foveal choriocapillary VD (P < 0.05). Conclusions: The severity of MfS correlates with the impairment of the retinal and choroidal vasculature. Translational Relevance: Optical coherence tomography angiography may be a reproducible and noninvasive tool to study retinal blood flow in patients with MfS, with potential diagnostic and prognostic value.

Is there a relationship between dopamine and rhegmatogenous retinal detachment?

Dopamine and its receptors have been widely studied in the neurological conditions and in the retina. In this study, we evaluated the possible role of dopamine in rhegmatogenous retinal detachment (RRD) by comparing the amount of 3,4-dihydroxyphenylacetic acid (DOPAC), a surrogate index of retinal dopamine levels, in the vitreous sample of patients affected by RRD with those affected by macular pucker and vitreous hemorrhage. Our results showed that significantly higher levels of DOPAC were found in the vitreous sample of patients affected by RRD compared with those affected by vitreous hemorrhage and macular pucker (P = 0.002). Specifically, no trace of the substance was found in vitreous hemorrhage and macular pucker samples. A slightly significant positive correlation was found among DOPAC and post-operative best corrected visual acuity (r = 0.470, P = 0.049). No correlation was found between DOPAC and the days elapsed between diagnosis and surgery (P = 0.317). For the first time our findings suggest that DOPAC is released in RRD, but not in other retinal diseases such as vitreous hemorrhage and macular pucker. Moreover, we showed a correlation between visual acuity outcome and the amount of DOPAC in the vitreous. This might have a potential, although still unknown, implication in the pathogenesis of the disease and/or in the associated photoreceptors loss. This study was approved by the Ethics Committee of Rome Tor Vergata University Hospital (R.S.92.10) on September 24, 2010.

Primary Open Angle Glaucoma Is Associated With Functional Brain Network Reorganization.

Background: Resting-state functional magnetic resonance imaging (rs-fMRI) is commonly employed to study changes in functional brain connectivity. The recent hypothesis of a brain involvement in primary open angle Glaucoma has sprung interest for neuroimaging studies in this classically ophthalmological pathology. Object: We explored a putative reorganization of functional brain networks in Glaucomatous patients, and evaluated the potential of functional network disruption indices as biomarkers of disease severity in terms of their relationship to clinical variables as well as select retinal layer thicknesses. Methods: Nineteen Glaucoma patients and 16 healthy control subjects (age: 50-76, mean 61.0 ± 8.2 years) underwent rs-fMRI examination at 3T. After preprocessing, rs-fMRI time series were parcellated into 116 regions using the Automated Anatomical Labeling atlas and adjacency matrices were computed based on partial correlations. Graph-theoretical measures of integration, segregation and centrality as well as group-wise and subject-wise disruption index estimates (which use regression of graph-theoretical metrics across subjects to quantify overall network changes) were then generated for all subjects. All subjects also underwent Optical Coherence Tomography (OCT) and visual field index (VFI) quantification. We then examined associations between brain network measures and VFI, as well as thickness of retinal nerve fiber layer (RNFL) and macular ganglion cell layer (MaculaGCL). Results: In Glaucoma, group-wise disruption indices were negative for all graph theoretical metrics. Also, we found statistically significant group-wise differences in subject-wise disruption indexes in all local metrics. Two brain regions serving as hubs in healthy controls were not present in the Glaucoma group. Instead, three hub regions were present in Glaucoma patients but not in controls. We found significant associations between all disruption indices and VFI, RNFL as well as MaculaGCL. The disruption index based on the clustering coefficient yielded the best discriminative power for differentiating Glaucoma patients from healthy controls [Area Under the ROC curve (AUC) 0.91, sensitivity, 100%; specificity, 78.95%]. Conclusions: Our findings support a possible relationship between functional brain changes and disease severity in Glaucoma, as well as alternative explanations for motor and cognitive symptoms in Glaucoma, possibly pointing toward an inclusion of this pathology in the heterogeneous group of disconnection syndromes.

Bioavailability and Sustained Plasma Concentrations of CoQ10 in Healthy Volunteers by a Novel Oral Timed-Release Preparation.

Coenzyme Q10 (CoQ10) is a natural compound with potent antioxidant properties. Its provision through diet does not always allow adequate levels in the human body, and supplementation is often necessary. This bioavailability study intended to explore the plasma concentration levels of a novel CoQ10 oral preparation (COQUN®, Coenzyme Q10 Miniactives Retard 100 mg capsules) mimicking assumption on a regular basis. Twenty-four healthy adults tested a single dose of CoQ10 100 mg in one day to assess bioavailability. After a one week wash-out period, they were randomly assigned (1:1) to continuous administration for four weeks: Group A (n = 12) 100 mg once a day (OD); and Group B (n = 12) 100 mg twice a day (BID). During the single dose phase, Cmax was observed at 4 h, and the mean values of AUCt and Tmax were 8754 µg/mL·h and 4.29 h, respectively. The multiple dose phase showed increasing plasma levels up to 7 days after the start of administration, and sustained high concentrations during the all administration period. No relevant adverse events were reported. These results show that Miniactives® technology can release CoQ10 to allow high constant blood concentrations without a sharp decrease. This may be the first step of evidence for a potential new antioxidative treatment in human chronic diseases deserving high CoQ10 levels.

Disruption of brain network organization in primary open angle glaucoma.

Resting-state functional magnetic resonance imaging (rs-fMRI) is commonly employed to study changes in functional brain connectivity. Recently, the hypothesis of a brain involvement in primary open angle glaucoma has sprung interest for neuroimaging studies in this pathology. The purpose of this study is to evaluate a putative reorganization of brain networks in glaucomatous patients through graph-theoretical measures of integration, segregation and centrality by exploiting a multivariate networks association measure and a recently introduced global and local brain network disruption index. Nineteen glaucoma patients and sixteen healthy control subjects (age: 50 - 76, mean 61 years) underwent rs-fMRI examination at 3T. After preprocessing, rs-fMRI time series were parcellated into 116 regions (AAL atlas), adjacency matrices were computed based on partial correlations and graph-theoretical measures of integration, segregation and centrality as well as group-wise and subject-wise disruption index estimates were generated for all subjects. We found that the group-wise disruption index was negative and statistically different from 0 in for all graph theoretical metrics. Additionally, statistically significant group-wise differences in subject-wise disruption indexes were found in all local metrics. The differences in local network measures highlight cerebral reorganization of brain networks in glaucoma patients, supporting the interpretation of glaucoma as central nervous system disease, likely part of the heterogeneous group of recently described disconnection syndromes.

Neurodegenerative Process Linking the Eye and the Brain.

Recent literature agrees that neurodegenerative processes involve both the retina and the central nervous system, which are two strictly related anatomical structures. However, the causal mechanisms of this dual involvement are still uncertain. To date, anterograde transsynaptic neurodegeneration, triggered by retinal ganglion cells' death, and retrograde transsynaptic neurodegeneration, induced by neurodegenerative processes of the central nervous system, has been considered the major possible causal mechanisms. The development of novel neuroimaging techniques has recently supported both the study of the central stations of the visual pathway as well as the study of the retina which is possibly an open window to the central nervous system.