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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., (© 2020 Elsevier B.V. All rights reserved.)

Background: glaucoma is the leading cause of irreversible blindness all over the world. The degree of visual field loss accounts for the severity of the disease and represents the main clinical outcome of treatment for patients affected by glaucoma. The α2 agonists, like brimonidine, emerged in the 1960s as topical ophthalmologic treatment. Their neuroprotective mechanism in glaucoma is still debated, ranging from effect on extracellular glutamate, to ocular hypotension and blood flow., Objectives: this systematic review and meta-analysis aims at assessing the efficacy of brimonidine on visual field deterioration during glaucoma through the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) approach. Databases consulted: the literature search has been performed on PubMed, MEDLINE, ClinicalTrials.gov and Scopus up to June 10th, 2020. Study eligibility criteria, participants, and interventions: clinical trials assessing the effects of brimonidine on visual field in patients with glaucoma. Study appraisal: the eligibility of the studies has been assessed by two independent authors and the selection has followed the PRISMA flow diagram. The retrieved results have been subjected to risk of bias evaluation., Results: the search of literature has retrieved 418 papers, among which 5 are eligible for inclusion in the qualitative analysis. All the studies present high heterogeneity, therefore meta-analysis has not been possible. The results obtained suggest that brimonidine improves visual field, but the design of the clinical trials rises some concerns in terms of risk of bias., Conclusions: the evidence of neuroprotective effect of brimonidine is inconclusive and needs stronger support. Large double-blind randomized clinical trials are necessary to strengthen this evidence., Competing Interests: Conflicts of interest The authors declare no conflict of interest., (© 2020 Elsevier B.V. All rights reserved.)

Background: glaucoma is a remarkable social issue being the leading cause of irreversible blindness worldwide. It is a progressive neuropathy characterized by the death of the retinal ganglion cells, of which the most important risk factor is represented by the increase of intraocular pressure (IOP). The role of nutraceutical supplementations with anti-oxidant activity has been extensively tested in preclinical models of glaucoma. The clinical efficacy of nutraceuticals in glaucoma is still controversial., Objectives: the aim of this systematic review is to assess the efficacy of nutraceuticals with anti-oxidant activity in glaucoma through the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) rigorous criteria., Data Sources: the literature search has been performed on the electronic databases currently recognized of most relevance for medical scientific literature, i.e. PubMed, MEDLINE, The Cochrane Central Register of Controlled Trials (CENTRAL) with access to EMBASE, ClinicalTrials.gov and Scopus. The date of last search is April 8th, 2020. Study eligibility criteria, participants, and interventions: prospective randomized clinical trials assessing the effects of nutraceuticals and anti-oxidants on IOP and/or visual field in patients with glaucoma. The eligible papers must be published in English and available in full text., Study Appraisal and Synthesis Methods: the evaluation of the eligibility of the studies has been carried out independently by two authors. The selection process has followed the PRISMA flow diagram, assessing the quality of the body of evidence and the risk of bias., Results: the search of literature has retrieved 1615 papers and 2 clinical trials with results, among which only 6 are eligible for inclusion in the present systematic review to address the preset participants, interventions, comparisons, outcomes and study design (PICOS) "are the nutraceuticals effective in glaucoma?". In 5 out of 6 studies the nutraceutical supplementation is effective in providing additional decrease of IOP to current usual therapy, without the occurrence of side effects. However, all the studies present high heterogeneity and some concerns in terms of risk of bias, apart from one trial for which the risk of bias is low., Conclusions: the evidence of effectiveness of nutraceutical formulations is still uncertain and inconclusive. Therefore, large double-blind randomized clinical trials with adequate design, methodology and statistical power are needed to support the use of nutraceuticals in glaucoma., Competing Interests: Conflicts of interest The authors declare no conflict of interest., (© 2020 Elsevier B.V. All rights reserved.)

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., Competing Interests: Disclosure statement The authors declare no potential conflicts of interest exist., (© 2020 Elsevier B.V. All rights reserved.)

Glaucoma is the most common neurodegenerative cause of irreversible blindness worldwide. Restricted caloric regimens are an attractive approach for delaying the progression of neurodegenerative diseases. Here we review the current literature on the effects of caloric restriction on retinal neurons, under physiological and pathological conditions. We focused on autophagy as one of the mechanisms modulated by restricted caloric regimens and involved in the death of retinal ganglion cells (RGCs) over the course of glaucoma., (© 2020 Elsevier B.V. All rights reserved.)

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., Competing Interests: Conflicts of interest None., (© 2020 Elsevier B.V. All rights reserved.)

Glaucoma is an optic neuropathy that can result in progressive and irreversible vision loss, thereby affecting quality of life (QoL) of patients. Several studies have shown a strong correlation between visual field damage and visual disability in patients with glaucoma, even in the early stages of the disease. Visual impairment due to glaucoma affects normal daily activities required for independent living, such as driving, walking, and reading. There is no generally accepted instrument for assessing quality of life in glaucoma patients; different factors involved in visual disability from the disease are difficult to quantify and not easily standardized. This chapter summarizes recent works from clinical and epidemiological studies, which describe how glaucoma affects the performance of important vision-related activities and QoL., (© 2015 Elsevier B.V. All rights reserved.)

Glaucoma is the leading cause of irreversible blindness worldwide. Although the intraocular pressure (IOP) has been considered for long time the key point and the only treatable risk factor of the disease, there are cases in which glaucoma continues to progress despite normal IOP values. Vision loss in glaucoma is related to a selective decrease in the number of retinal ganglion cells by apoptosis that is associated to alterations of the central visual pathways. Interestingly, similar events have been also described in disorders of the central nervous system (CNS), such as Alzheimer's disease, Parkinson's disease, Leber's hereditary optic neuropathy, and cerebrovascular diseases. In this review, we discuss recent evidence supporting pathological links between glaucoma and disorders of the CNS., (© 2015 Elsevier B.V. All rights reserved.)

Glaucoma, the second leading cause of blindness in the world, is a chronic optic neuropathy often associated with increased intraocular pressure and characterized by progressive retinal ganglion cell (RGC) axons degeneration and death leading to typical optic nerve head damage and distinctive visual field defects. Although the pathogenesis of glaucoma is still largely unknown, it is hypothesized that RCGs become damaged through various insults/mechanisms, including ischemia, oxidative stress, excitotoxicity, defective axonal transport, trophic factor withdrawal, and neuroinflammation. In this review, we summarize the potential benefits of several natural compounds for RGCs neuroprotection., (© 2015 Elsevier B.V. All rights reserved.)

Recent advances in Magnetic Resonance Imaging (MRI) technology have brought new insight in central nervous system (CNS) manifestation of glaucoma. New MR techniques allowed to identify in vivo and noninvasively alterations along all the visual pathway in both early and late stages of the disease. Conventional neuroimaging still plays an important role, mostly in the anatomy description and in the differential diagnosis with space occupying lesions but it should be supported by other advanced MR techniques such as diffusion tensor imaging, functional imaging (BOLD-ASL), and magnetic resonance spectroscopy, which offer the possibility to investigate deep white matter tracts integrity and cortical gray matter changes. In a future perspective, MR quantification of CNS damage associated with glaucoma will be of pivotal importance for prognostic stratification and evaluation of neuroprotective therapy response., (© 2015 Elsevier B.V. All rights reserved.)

Glaucoma is a neurodegenerative disease caused by the progressive apoptotic death of retinal ganglion cells (RGCs). The mechanisms leading to the RGC loss are still unknown but it is now clear that, besides elevated intraocular pressure (IOP), which is considered the main risk factor, other IOP-independent determinants are responsible for the development of the optic neuropathy. Autophagy is a highly conserved catabolic pathway by which cellular components are degraded through the lysosomes. Dysfunctional autophagic pathway has been associated with several neuropathological conditions and a considerable number of studies have proved autophagy as a potential target for pharmacological modulation to achieve neuroprotection. Here, we review the current literature bridging the degeneration of RGCs to alterations of the autophagic pathway; we also discuss the possible role of autophagy in the pathogenesis and progression of glaucoma in view of the future application of autophagy modulators for glaucoma therapy., (© 2015 Elsevier B.V. All rights reserved.)

Recently developed neuroimaging techniques such as diffusion tensor (DT) magnetic resonance (MR) imaging, functional MR imaging (fMRI), and MR spectroscopy can be used to evaluate the microstructural integrity of white-matter fibers and the functional activity of gray matter. They have been widely employed to investigate various diseases of the central nervous system, and they can be useful tools for assessing the integrity and functional connections of the visual pathways and areas that play key roles in glaucoma. In vivo degeneration of the optic nerves can be noninvasively demonstrated by DT MR imaging. DT fiber tractography provides valuable information on the axonal density of postgeniculate fibers (optic radiation), and fMRI studies of patients with primary open-angle glaucoma (POAG) have demonstrated alterations involving the human visual cortex that are consistent with clinically documented losses of visual function. This article reviews some of the more recent data supporting the use of MR imaging techniques as reliable, noninvasive tools for monitoring the progression of human glaucoma.

Certain general conclusions can be drawn from a series of 56 studies on glaucoma prevalence. Even in the most recently published studies the rate of undiagnosed glaucoma is particularly high. Another fairly constant finding is the discrepancy between the clinical and epidemiologic diagnoses of glaucoma. The prevalence of primary open-angle glaucoma (POAG) has been increasing, and this trend is undoubtedly due at least in part to advances in diagnostic technology. The decreasing prevalence of primary angle-closure glaucoma (PACG) is due to the adoption of more stringent criteria for the diagnosis of this form of glaucoma. Prevalence increases proportionately with age for each racial group. African or African origin populations had the highest POAG prevalence at all ages but the increase in prevalence of POAG is steeper for white populations. PACG is commonest in Asian ethnic groups, with the exception of the Japanese. Low-tension glaucoma (LTG) is quite common in the Japanese population. Over 80% of those with PACG live in Asia, while POAG disproportionately affects those of African derivation. Women are more affected by glaucoma. Very few incidence studies have been completed, because the cost of examining large samples is high. There are only two recent studies conducted on persons of African descent in Barbados (West Indies) and on white inhabitants of Rotterdam (Netherlands). Risk of incident glaucoma was highest among persons classified as having suspect POAG at baseline, followed by those with ocular hypertension. No difference in incidence of POAG between men and women was found. The more recent studies which included routine visual-field testing reveal rates of blinding glaucoma <10% in many countries, including those that are developing.