Search

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., Competing Interests: The authors declare no conflicts of interest.

Background: The endocannabinoid system (ECS) is a complex biological regulatory system. Its expression and functionality have been widely investigated in ocular tissues. Recent data have reported its modulation to be valid in determining an ocular hypotensive and a neuroprotective effect in preclinical animal models of glaucoma., Aim: This study aimed to explore the available literature on cannabinoid receptor 1 (CB 1 R), cannabinoid receptor 2 (CB 2 R), and transient receptor potential vanilloid 1 (TRPV1) expression in the trabecular meshwork (TM), ciliary body (CB), and retina as well as their ocular hypotensive and neuroprotective effects in preclinical, in vivo, animal glaucoma models., Materials and Methods: The study adhered to both PRISMA and SYRCLE guidelines. Sixty-nine full-length articles were included in the final analysis., Results: Preclinical studies indicated a widespread distribution of CB 1 R, CB 2 R, and TRPV1 in the TM, CB, and retina, although receptor-, age-, and species-dependent differences were observed. CB 1 R and CB 2 R modulation have been shown to exert ocular hypotensive effects in preclinical models via the regulation of inflow and outflow pathways. Retinal cell neuroprotection has been achieved in several experimental models, mediated by agonists and antagonists of CB 1 R, CB 2 R, and TRPV1., Discussion: Despite the growing body of preclinical data regarding the expression and modulation of ECS in ocular tissues, the mechanisms responsible for the hypotensive and neuroprotective efficacy exerted by this system remain largely elusive. Research on this topic is advocated to further substantiate the hypothesis that the ECS is a new potential therapeutic target in the context of glaucoma., (Copyright © 2022. Published by Elsevier Masson SAS.)

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., Competing Interests: Conflict of interest statement Nothing declared., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Glaucoma, a leading cause of irreversible blindness worldwide, is an optic neuropathy characterized by the progressive death of retinal ganglion cells (RGCs). Elevated intraocular pressure (IOP) is recognized as the main risk factor. Despite effective IOP-lowering therapies, the disease progresses in a significant number of patients. Therefore, alternative IOP-independent strategies aiming at halting or delaying RGC degeneration is the current therapeutic challenge for glaucoma management. Here, we review the literature on the neuroprotective activities, and the underlying mechanisms, of natural compounds and dietary supplements in experimental and clinical glaucoma.

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, specifically a neurodegenerative disease characterized by loss of retinal ganglion cells (RGCs) and their axons. The pathogenesis of RGC loss in glaucoma remains incompletely understood and a broad range of possible mechanisms have been implicated. Clinical evidence indicates that lowering intraocular pressure (IOP) does not prevent progression in all patients; therefore, risk factors other than those related to IOP are involved in the disease. The need for alternative, non-IOP-lowering treatments focused at preventing progression, that is, neuroprotectants, has become of interest to both the patient and the physician. Experimental evidence accumulated during the past two decades lend a great deal of support to molecules endowed with neuroprotective features. However, translation to the clinic of the latter drugs results unsuccessful mostly because of the lack of reliable in vivo measure of retinal damage, thus hampering the good therapeutic potential of neuroprotective agents given alone or as adjuvant therapy to IOP-lowering agents. Further research effort is needed to better understand the mechanisms involved in glaucoma and the means to translate into clinic neuroprotective drugs.

Background: Open Angle Glaucoma (POAG) is the leading causes of irreversible blindness worldwide. Elevated intraocular pressure is considered an important risk factor for glaucoma; however, a subset of patients experiences a progression of the disease even in presence of normal intraocular pressure values. This implies that risk factors other than intraocular pressure are involved in the pathogenesis of glaucoma. A possible relationship between glaucoma and neurodegenerative diseases such as Alzheimer Disease has been suggested. In this regard, we recently described a high prevalence of alterations typical of glaucoma, using Heidelberg Retinal Tomograph-3, in a group of patients with Alzheimer Disease. Interestingly, these alterations were not associated with elevated intraocular pressure or abnormal Central Corneal Thickness values. Alzheimer Disease is the most common form of dementia with progressive deterioration of memory and cognition. Complaints related to vision are common among Alzheimer Disease patients., Methods: In this paper researches related to glaucoma and Alzheimer disease are reviewed., Results: Diseases characteristics, i.e. common features, risk factors and pathophysiological mechanisms gathered in the recent literature do suggest that Alzheimer Disease and glaucoma can be considered both age-related neurodegenerative diseases that may co-exist in the elderly., Conclusion: In conclusion, preclinical and clinical evidence gathered so far support the notion that glaucoma is a widespread neurodegenerative condition whose common pathogenetic mechanisms with other diseases, i.e. Alzheimer Disease, should be further investigated as they may shed new light on these diseases improving both diagnosis and treatments., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Glaucoma is a disease where retinal ganglion cells (RGC) are specifically affected though a number of evidences endorse the hypothesis that glaucoma is a neuro-degenerative disorder of the central nervous system and suggest a possible connection between glaucomatous damage and cerebrovascular alterations. The mechanisms underlying RGC loss are not yet fully known but alterations of the autophagy machinery have been recently proposed as a potential contributing factor as for Alzheimer's disease. Here we review the current literature on new strategies for neuroprotection in glaucoma, focusing on pharmacologic strategies to minimize RGC damage., (Copyright © 2016 Elsevier B.V. All rights reserved.)

In clinical glaucoma, as well as in experimental models, the loss of retinal ganglion cells occurs by apoptosis. This final event is preceded by inflammatory responses involving the activation of innate and adaptive immunity, with retinal and optic nerve resident glial cells acting as major players. Here we review the current literature on the role of neuroinflammation in neurodegeneration, focusing on the inflammatory molecular mechanisms involved in the pathogenesis and progression of the optic neuropathy., (Copyright © 2016 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.)

The aim of this study was to evaluate pupillary response to light stimulation in patients with different stages of glaucoma using computerized pupillometry. We conducted a retrospective study on a group of 44 glaucoma patients who had undergone complete ophthalmological examination, visual field test (Humphrey SITA Standard 24-2) and monocular dynamic pupillometry (MonCV3 Metrovision). Eyes were classified into stages of glaucoma according to visual field damage using the Glaucoma Staging System 2. A group of 18 healthy subjects, homogeneous for age and sex with glaucoma patients, was used as a control. The following parameters were considered-latency and duration of contraction and dilatation; initial, minimum, maximum, and mean pupil diameter; amplitude of contraction; contraction and dilatation speed; and percent pupil contraction (PPC). PPC and pupil contraction speed and minimum diameter showed covariate correlation with the stages of glaucoma. The control group significantly differed from the stage 3 group in terms of PPC and from the stage 4 group in terms of minimum diameter. There were significant differences between the stage 5 group and stage 1, 2, 3 and control groups. Ordinal logistic regression showed a correlation between pupil contraction speed, minimum diameter, PPC, initial diameter and the stage of glaucoma. The study showed that glaucoma damage is associated with altered values of pupillary response to light. This event may be the consequence of the progressive loss of retinal ganglion cells and their axons induced by glaucoma.

Purpose: To evaluate the levels of malondialdehyde (MDA) and total antioxidant capacity (TAC) in the blood and aqueous humor of glaucomatous and nonglaucomatous patients. To measure the adenosine triphosphate/adenosine diphosphate/adenosine monophosphate (ATP/ADP/AMP) concentration as a biomarker of the blood energy charge potential., Methods: We examined 40 consecutive patients with primary open-angle glaucoma scheduled for cataract surgery. Twenty-six age-matched subjects scheduled for cataract surgery were enrolled as a control group. Blood and aqueous humor samples were collected at the time of surgery. MDA concentrations and blood nucleotides were measured with high-performance liquid chromatography. The TAC of the samples was estimated with the oxygen-radical absorbance capacity method., Results: Blood and aqueous humor MDA levels in glaucoma patients (respectively, 0.976±0.370 and 0.145±0.065 μmol/ml) were significantly increased (p<0.001 for both) over those of the control group (respectively, 0.454±0.395 and 0.060±0.039 μmol/ml). In contrast, the control group presented significantly higher TACs than did the glaucoma group in both the blood (control: 2.681±1.101 and glaucoma: 1.617±0.674 μmol Trolox Equi/g; p<0.001) and aqueous humor (control: 0.963±0.302 and glaucoma: 0.788±0.346 μmol Trolox Equi/g; p=0.039). The control group (0.869±0.037) exhibited statistically significant (p<0.001) higher values of blood adenosine triphosphate/adenosine diphosphate (ATP-ADP) levels than did the glaucoma group (0.791±0.037)., Conclusions: Our data further support the hypothesis that oxidative stress and decreased antioxidant defenses are involved in glaucoma. High-performance liquid chromatography appears to be an effective and sensitive method to detect altered levels of oxidative stress markers in glaucoma patients.

Autophagy is a highly conserved catabolic pathway in which proteins and organelles are engulfed by vacuoles that are targeted to lysosomes for degradation. Defects in the autophagic machinery have been described in several neurodegenerative diseases uncovering the tight dependency of neuronal survival on the efficiency of the autophagic process. Despite the large amount of literature investigating autophagy in a number of pathological conditions our knowledge of its role in glaucoma neurodegeneration is just beginning. However, recent experimental data revealing that autophagy modulation occurs in retinal ganglion cells (RGCs) under glaucoma-related stressing conditions support the hypothesis that dysfunctional autophagy might underlie the process leading to RGC death. Although our understanding of the role of autophagy in glaucoma is still developing, there is the possibility that neuroprotection may be achieved by modulating autophagy. This would be a promising approach as it could lead to the much-sought development of alternative therapeutic strategies to prevent visual loss in glaucoma., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

On the basis of a large body of experimental data the notion that glaucoma damages retinal ganglion cells and central areas of the visual system has been put forward. The mechanisms underlying glaucomatous involvement of the central areas are not known: the most likely hypothesis is that this event is the result of an anterograde transynaptic neurodegeneration triggered by ganglion cells' death. However, it is possible that in some cases it may be the consequence of a neurodegenerative disease of the central nervous system. In any event, novel mechanisms leading to cell demise might be implicated. The development of powerful neuroimaging techniques in conjunction with sophisticated analysis has recently provided compelling support to the involvement of central stations of the visual pathway in patients suffering of glaucoma. Diffusion Tensor-MRI allows the central damage associated with glaucoma to be assessed and therapeutic efficacy of novel neuroprotective interventions to be quantified., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Purpose: To evaluate, with high-field-strength diffusion-tensor (DT) magnetic resonance (MR) imaging, the axonal architecture of the optic nerves and optic radiations in patients with glaucoma and determine whether DT MR imaging-derived parameters correlate with disease severity., Materials and Methods: The study was approved by the institutional review board. All participants provided written informed consent. Sixteen patients with primary open-angle glaucoma were examined. Glaucoma severity was clinically assessed with use of a six-stage system based on static threshold visual field parameters. Ten healthy individuals served as control subjects. DT MR imaging was performed with a 3-T MR unit. Mean diffusivity (MD) and fractional anisotropy (FA) maps were automatically created. Regions of interest were positioned on the MD and FA maps, and mean MD and mean FA values were calculated for each optic nerve and each optic radiation., Results: The optic radiations and optic nerves of patients with glaucoma, as compared with control subjects, had significantly higher MD and significantly lower FA. The mean MD values for the optic nerves and the glaucoma stages varied consistently (r = 0.8087, P < .0001). A negative correlation between mean FA for the optic nerves and glaucoma stage (r = -0.7464, P < .0001) was observed., Conclusion: Glaucoma is a complex neurologic disease that affects optic nerves and optic radiations. The finding that DT MR imaging-derived MD and FA in the optic nerves correlate with glaucoma severity suggests that these parameters could serve as complementary indicators of disease severity.

Excitotoxic neuronal death is a common feature of neurodegenerative and ischemic diseases of the central nervous system (CNS) and of a variety of ocular diseases, including glaucoma. Glaucoma, one of the leading causes of blindness in the world, is characterized by a progressive degeneration of retinal ganglion cells (RGCs) and their axons and is often associated with elevated intraocular pressure (IOP). Retinal ischemia/reperfusion induced by experimental elevation of IOP leads to damage and loss of RGCs. Under these conditions, structural, functional, and biochemical changes implicate the accumulation of extracellular glutamate and activation of the excitotoxic cascade. Beside the activation of associated pathways, death of RGCs is accompanied by impaired endogenous defenses, such as the PI3K/Akt prosurvival pathway. Original neurochemical and pharmacological evidence are discussed here to strengthen the role for excitotoxicity in RGCs death occurring in experimental, angle closure, glaucoma in conjunction with the discovery of novel molecular targets to potentiate endogenous prosurvival defenses in the glaucomatous retina.

Recent evidence shows that the endocannabinoid system is involved in the pathogenesis of numerous neurodegenerative diseases of the central nervous system. Pharmacologic modulation of cannabinoid receptors or the enzymes involved in the synthesis, transport, or breakdown of endogenous cannabinoids has proved to be a valid alternative to conventional treatment of these diseases. In this review, we will examine recent findings that demonstrate the involvement of the endocannabinoid system in glaucoma, a major neurodegenerative disease of the eye that is a frequent cause of blindness. Experimental findings indicate that the endocannabinoid system contributes to the control of intraocular pressure (IOP), by modulating both production and drainage of aqueous humor. There is also a growing body of evidence of the involvement of this system in mechanisms leading to the death of retinal ganglion cells, which is the end result of glaucoma. Molecules capable of interfering with the ocular endocannabinoid system could offer valid alternatives to the treatment of this disease, based not only on the reduction of IOP but also on neuroprotection.

Glaucoma is a worldwide leading cause of irreversible vision loss characterized by progressive death of retinal ganglion cells (RGCs). In the course of glaucoma, RGC death may be the consequence of energy impairment that triggers secondary excitotoxicity and free radical generation. There is substantial evidence also that a number of free radical scavengers and/or agents that improve mitochondrial function may be useful as therapies to ameliorate cell death in various neurological disorders including glaucoma. Coenzyme Q10 (CoQ10), an essential cofactor of the electron transport chain, has been reported to afford neuroprotection in neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases, and its protective effect has been attributed in part to its free radical scavenger ability and to a specific regulation of the mitochondrial permeability transition pore. Using an established animal model of transient retinal ischemia, we have conclusively identified a role for abnormal elevation of extracellular glutamate in the mechanisms underlying RGC death that occurs, at least in part, via activation of the apoptotic program. Under these experimental conditions, N-methyl-D-aspartate (NMDA) and non-NMDA subtype of glutamate receptor antagonists, nitric oxide synthase inhibitors, and CoQ10 afford retinal protection supporting an important role for excitotoxicity in the mechanisms underlying RGC death.

Background: Resource utilisation and direct costs associated with glaucoma progression in Europe are unknown. As population progressively ages, the economic impact of the disease will increase., Methods: From a total of 1655 consecutive cases, the records of 194 patients were selected and stratified by disease severity. Record selection was based on diagnoses of primary open angle glaucoma, glaucoma suspect, ocular hypertension, or normal tension glaucoma; 5 years minimum follow up were required. Glaucoma severity was assessed using a six stage glaucoma staging system based on static threshold visual field parameters. Resource utilisation data were abstracted from the charts and unit costs were applied to estimate direct costs to the payer. Resource utilisation and estimated direct cost of treatment, per person year, were calculated., Results: A statistically significant increasing linear trend (p = 0.018) in direct cost as disease severity worsened was demonstrated. The direct cost of treatment increased by an estimated 86 for each incremental step ranging from 455 euro per person year for stage 0 to 969 euro per person year for stage 4 disease. Medication costs ranged from 42% to 56% of total direct cost for all stages of disease., Conclusions: These results demonstrate for the first time in Europe that resource utilisation and direct medical costs of glaucoma management increase with worsening disease severity. Based on these findings, managing glaucoma and effectively delaying disease progression would be expected to significantly reduce the economic burden of this disease. These data are relevant to general practitioners and healthcare administrators who have a direct influence on the distribution of resources.

The lateral geniculate nucleus (LGN) is the thalamic relay of retinal inputs to the visual cortex. It contains a rich array of brain terminals, which modulate the visual signals to the cortex. Several data have documented that beside cholinergic, GABA-nergic, istaminergic, serotoninergic, and glutamatergic signals, the LGN contains also fibers and interneurons expressing the enzyme that produces nitric oxide (NO). Here, we review the documented physiological roles of NO in the transmission of visual inputs to the cortex and in the processes of activity-dependent refinement of LGN connections. Moreover we focus on the recently suggested role of NO in processes of neurotoxicity in the LGN. Particular relevance is given to studies documenting that, through an excitotoxic cascade, NO triggers apoptosis in the LGN of new-born rats deprived of vision in one eye. Data are also discussed on a possible role of NO in the mechanisms of LGN neuronal loss induced by glaucoma. We believe that a better understanding of the role of NO in the LGN may contribute to discover new experimental strategies for the treatment of degenerative ophthalmic diseases. [Copyright &y& Elsevier]