Disease Progression In Glaucoma Research Articles

Glaucoma, More than Meets the Eye: Patterns of Demyelination Revealed in Human Postmortem Glaucomatous Optic Nerve.

Glaucoma is a neurodegenerative disease affecting millions worldwide, characterised by retinal ganglion cell (RGC) degeneration which leads to blindness in more advanced cases. Although the pathogenesis and underlying mechanisms of glaucoma are not fully understood, there are theories that hint at demyelination playing a role in the disease process. Demyelination, or the degeneration of the myelin sheath surrounding axons, has been found in previous studies using animal models of glaucoma and clinical assessments of glaucoma patients. However, this has not been fully realised or quantified in glaucoma patients. Utilising postmortem optic nerve samples from glaucoma and healthy subjects, various immunohistochemical and morphological assessments were performed to determine the extent, if any, of demyelination in glaucomatous optic nerves. Our findings revealed that alongside nerve shrinkage and degeneration of nerve tissue fascicles, there were significantly less myelin proteins, specifically myelin basic protein (MBP), in glaucoma optic nerves. Additionally, the loss of MBP was correlated with decreased oligodendrocyte (OLG) precursors and increasing glial activity. This further supports previous evidence that demyelination may be a secondary degenerative process associated with glaucoma disease progression. Not only do these results provide evidence for potential disease mechanisms, but this is also the first study to quantify optic nerve demyelination in glaucoma postmortem tissue.

Glaucoma and the Human Microbiome.

To explore a view of the human microbiome as an interconnected, functional, dynamic system that may be linked to the pathogenesis and progression of glaucoma. A literature review was undertaken that included publications from 1966 to 2023. Bacterial lipopolysaccharides (LPS) activate toll-like receptors (TLR) and mediate the human immune response. The LPS-TLR4 pathway is a potential avenue for the ocular, gut, and oral microbiomes to interface and/or influence ocular disease. Studies of gut dysbiosis have shown that alterations in the healthy microbiota can predispose the host to immune-mediated inflammatory and neurodegenerative conditions, while oral and ocular surface dysbiosis has been correlated with glaucoma. While developmental exposure to commensal microflora has shown to be necessary for the autoimmune and neurodegenerative responses to elevated intraocular pressure to take place, commensal bacterial products like short-chain fatty acids have regulatory effects protective against glaucoma. Alterations to human microbiotas have been associated with changes in intestinal permeability, gene regulation, immune cell differentiation, and neural functioning, which may predispose the host to glaucoma. Select microbes have been highlighted for their potential contributions to glaucoma disease progression or protection, raising the potential for microbiota-based treatment modalities. Current topical glaucoma treatments may disrupt the ocular surface microbiota, potentially having ramifications on host health. Further study of the relationships between human microbiome and glaucoma is needed.

Glaucoma, More than Meets the Eye: Patterns of Demyelination Revealed in Human Postmortem Glaucomatous Optic Nerve.

Glaucoma is a neurodegenerative disease affecting millions worldwide, characterised by retinal ganglion cell (RGC) degeneration which leads to blindness in more advanced cases. Although the pathogenesis and underlying mechanisms of glaucoma are not fully understood, there are theories that hint at demyelination playing a role in the disease process. Demyelination, or the degeneration of the myelin sheath surrounding axons, has been found in previous studies using animal models of glaucoma and clinical assessments of glaucoma patients. However, this has not been fully realised or quantified in glaucoma patients. Utilising postmortem optic nerve samples from glaucoma and healthy subjects, various immunohistochemical and morphological assessments were performed to determine the extent, if any, of demyelination in glaucomatous optic nerves. Our findings revealed that alongside nerve shrinkage and degeneration of nerve tissue fascicles, there were significantly less myelin proteins, specifically myelin basic protein (MBP), in glaucoma optic nerves. Additionally, the loss of MBP was correlated with decreased oligodendrocyte (OLG) precursors and increasing glial activity. This further supports previous evidence that demyelination may be a secondary degenerative process associated with glaucoma disease progression. Not only do these results provide evidence for potential disease mechanisms, but this is also the first study to quantify optic nerve demyelination in glaucoma postmortem tissue.

From bench to behaviour: The role of lifestyle factors on intraocular pressure, neuroprotection, and disease progression in glaucoma.

Current glaucoma management centres on intraocular pressure (IOP) reduction through pharmacological and surgical therapy. Despite broad interest in active management of glaucoma through lifestyle modifications, such recommendations have yet to be incorporated into standards of treatment. In this review, noteworthy preclinical studies and their translations in clinical populations are discussed to evaluate the roles of lifestyle factors in lowering IOP, offering neuroprotection, and/or slowing disease progression in those with open-angle glaucoma. Current literature suggests that aerobic exercise may be associated with neuroprotection and decreased disease progression. Mindfulness is associated with IOP reductions and neuroprotection. Caffeine is associated with mild, transient IOP elevations of uncertain significance. Nicotinamide supplementation is associated with neuroprotection and short-term visual function improvement. This review also highlights knowledge gaps regarding these factors and opportunities to strengthen our understanding of their role in glaucoma, including future preclinical studies that elucidate underlying mechanisms and clinical studies with additional functional endpoints and longer follow-up.

Long-term and potent IOP-lowering effect of IκBα-siRNA in a nonhuman primate model of chronic ocular hypertension

SummaryGlaucoma is one of the most common causes of irreversible blindness. It is acknowledged that lowering intraocular pressure (IOP) is the effective treatment to slow glaucoma disease progression. The main obstacle of existing drugs is that the effect of reducing IOP does not last long. Degradation of IκB stimulates the transcription of NF-κB, which could upregulate the expression of matrix metalloproteinases (MMPs). Whether a IκB-targeted gene therapy works in glaucoma is unclear. Here, we established a chronic ocular hypertension (COHT) model in rhesus monkey by laser photocoagulation and verified that intracameral delivery of IκBα-siRNA showed long-lasting and potent effects of reducing IOP without obvious inflammation in monkeys with COHT. We also verified that IκBα-siRNA could increase the expressions of MMP2 and MMP9 by knocking down IκBα in vitro and in vivo. Our results in nonhuman primates indicated that IκBα-siRNA may become a promising therapeutic approach for the treatment of glaucoma.

Lymphatics in Eye Fluid Homeostasis: Minor Contributors or Significant Actors?

Simple SummaryThe eye contains fluid compartments whose tight regulation is essential for proper eye functioning. Lymphatic vessels are known to be important in several physiological functions including interstitial fluid homeostasis. Recent works has provided evidence of a potential role of lymphatic vessels in the drainage of ocular fluids. They may in particular contribute to the intraocular pressure regulation, whose increase is a major risk factor for the progression of glaucoma, an eye disease that can lead to blindness. They could also participate in the clearance of toxic waste products responsible for eye retinal neurodegenerative processes. In this review, we performed an update of ocular lymphatic vessel distribution, of their mechanisms of development and of their role in aqueous humor drainage and eye fluid regulation. We discussed these data and made some proposals to elucidate unresolved questions to improve knowledge concerning the lymphatic vessels roles in ocular fluid regulation, which could have repercussions in eye disease therapeutic strategies.Lymphatic vessels exert major effects on the maintenance of interstitial fluid homeostasis, immune cell trafficking, lipid absorption, tumor progression and metastasis. Recently, novel functional roles for the lymphatic vasculature have emerged, which can be associated with pathological situations. Among them, lymphatics have been proposed to participate in eye aqueous humor drainage, with potential consequences on intraocular pressure, a main risk factor for progression of glaucoma disease. In this review, after the description of eye fluid dynamics, we provide an update on the data concerning the distribution of ocular lymphatics. Particular attention is given to the results of investigations allowing the three dimensional visualization of the ocular surface vasculature, and to the molecular mechanisms that have been characterized to regulate ocular lymphatic vessel development. The studies concerning the potential role of lymphatics in aqueous humor outflow are reported and discussed. We also considered the novel studies mentioning the existence of an ocular glymphatic system which may have, in connection with lymphatics, important repercussions in retinal clearance and in diseases affecting the eye posterior segment. Some remaining unsolved questions and new directions to explore are proposed to improve the knowledge about both lymphatic and glymphatic system interactions with eye fluid homeostasis.

Cardiovascular Disease Predicts Structural and Functional Progression in Early Glaucoma

To investigate the association between cardiovascular disease and baseline structural defects and disease progression in glaucoma. Prospective, longitudinal study of preperimetric and perimetric glaucoma. Two thousand six hundred twenty-eight eyes from 1314 participants recruited to the Progression Risk of Glaucoma: Relevant SNPs with Significant Association (PROGRESSA) study were evaluated for baseline and longitudinal structural thinning using spectral-domain OCT and for visual field progression on Humphrey visual field (HVF) assessment. Patients were classified as either predominantly macula ganglion cell-inner plexiform layer (mGCIPL), predominantly peripapillary retinal nerve fiber layer (pRNFL), or both mGCIPL and pRNFL structural change at enrollment, and then evaluated for longitudinal OCT or HVF progression. Cardiovascular disease and medication characteristics of the participants were compared with a reference group of stable patients. OCT and HVF baseline status and longitudinal progression. After accounting for age and cardiovascular characteristics, patients with predominantly mGCIPL thinning at baseline showed a higher prevalence of hypertension (odds ratio [OR], 2.70; 95% confidence interval [CI], 1.66-4.41; P < 0.001), antihypertensive use (OR, 2.03; 95% CI, 1.20-3.46; P= 0.008), and statin use (OR, 1.98; 95% CI, 1.07-3.66; P= 0.029) than reference patients. Patients with predominantly pRNFL thinning exhibited a comparable prevalence of cardiovascular disease or medication with reference patients. Review of longitudinal OCT and HVF data (mean follow-up, 5.34 ± 1.29 years) showed that hypertension was associated with an increased risk of both OCT (OR, 1.79; 95% CI, 1.17-2.75; P= 0.006) and HVF progression (OR, 1.92; 95% CI, 1.18-3.15; P= 0.013). A 1-standard deviation (approximately 21 mmHg) increase in systolic blood pressure at baseline was associated with a greater risk of OCT progression (OR, 1.27; 95% CI, 1.01-1.63; P=0.041) and HVF progression (OR, 1.32; 95% CI, 1.01-1.73; P= 0.043). The association between systolic blood pressure and structural progression was comparable to that observed between intraocular pressure and structural progression (OR, 1.30; 95% CI, 1.01-1.67; P= 0.039). Cardiovascular disease is an important risk factor for glaucoma progression.

The Evaluation of Retinal Nerve Fiber Layer and Ganglion Cell Complex Thickness in Adult Offspring of Primary Open-angle Glaucoma Patients.

In the adult offspring of glaucoma patients, retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thickness, especially in the inferior quadrant, were significantly decreased. This finding in the adult offspring of glaucoma patients may be important in evaluating the course of glaucoma disease. The aim of this study was to investigate RNFL and GCC thickness in adult offspring of primary open-angle glaucoma (POAG) patients and to compare the results with individuals without a family history for glaucoma disease. This was a cross-sectional observational study. Forty eyes of 40 individuals with self-reported family history for proven POAG and 40 eyes of 40 healthy individuals without a family history for glaucoma disease were included in the study. RNFL and macular GCC thickness were measured by spectral-domain optical coherence tomography, and the results were compared between the 2 groups. In adult offspring of patients with POAG, RNFL and GCC thickness were thinner in all quadrants. Average RNFL and GCC decreased significantly in adult offspring of patients with POAG (P=0.039 and 0.015, respectively). Thinning in RNFL and GCC thickness was especially significant in the inferior quadrant (P=0.024 and 0.039, respectively). There was no significant difference between the groups in terms of mean deviation and pattern standard deviation values (P=0.064 and 0.091, respectively). In adult offspring of POAG patients, especially in the inferior quadrant, the RNFL and GCC thickness are significantly lower than in subjects without a family history. Prospective, controlled clinical trials with longer follow-up are needed to better understand whether these changes are an early indicator of glaucoma, and the progression of glaucoma disease.

A spatially varying change points model for monitoring glaucoma progression using visual field data

Glaucoma disease progression, as measured by visual field (VF) data, is often defined by periods of relative stability followed by an abrupt decrease in visual ability at some point in time. Determining the transition point of the disease trajectory to a more severe state is important clinically for disease management and for avoiding irreversible vision loss. Based on this, we present a unified statistical modeling framework that permits prediction of the timing and spatial location of future vision loss and informs clinical decisions regarding disease progression. The developed method incorporates anatomical information to create a biologically plausible data-generating model. We accomplish this by introducing a spatially varying coefficients model that includes spatially varying change points to detect structural shifts in both the mean and variance process of VF data across both space and time. The VF location-specific change point represents the underlying, and potentially censored, timing of true change in disease trajectory while a multivariate spatial boundary detection structure is introduced that accounts for the complex spatial connectivity of the VF and optic disc. We show that our method improves estimation and prediction of multiple aspects of disease management in comparison to existing methods through simulation and real data application. The R package spCP implements the new methodology.

The role of optical coherence tomography angiography in early detection of primary open-angle glaucoma

Introduction Glaucoma is a slowly progressive disease with characteristic optic nerve abnormalities caused by accelerated ganglion cell complex (GCC) loss and concomitant retinal nerve fiber layer (RNFL) thinning. Glaucoma suspects are the key group to identify and treat with intraocular pressure lowering therapy in an effort to prevent blindness. Aim Determination and correlation of the role of the whole image, peripapillary, and inside disk vascular density (%) (wiVD%, ppVD%, and idVD%) in the RNFL of optic nerve head by optical coherence tomography angiography (OCT-A) and their correlation to GCC and RNFL thickness by OCT in early detection of preperimetric primary open-angle glaucoma. Patients and methods This prospective, nonrandomized, noninvasive, and observational case–control study was performed at the Ophthalmology Department and clinics of Al-Zahraa University Hospital, Al-Azhar University. It included 46 eyes of 23 participants who were divided into two groups: group I (control) consisted of 20 eyes of 10 healthy eyes. Group II (glaucoma suspects) consisted of 26 eyes of 13 preperimetric glaucoma suspects of the same age group. The peripapillary and inside disk optic nerve head vessel density were measured. Clinical data, visual field (VF) parameters, and spectral-domain OCT evaluation (RNFL thickness, GCC thickness, and rim area) were recorded. Results Significant decreases were found in whole image, peripapillary, and inside disk vascular density (%) and RNFL thickness especially in the temporal side, GCC, VF mean deviation, and VF index in suspected eyes than the normal eyes indicating the presence of early vascular changes in glaucoma. Conclusion OCT-A is a novel, noninvasive imaging technology that detects vascular changes as early signs in glaucoma disease progression; reduced vessel density also was associated with thinning of RNFL, and decrease in GCC count in a majority of cases. So, the diagnostic ability of OCT-A is a promising tool for early diagnosis of glaucoma.

Evaluation of optic nerve subarachnoid space in primary open angle glaucoma using ultrasound examination.

ObjectivesTo measure Optic Nerve Subarachnoid Space (ONSAS) in patients with primary open-angle glaucoma (POAG) and controls using A-scan ultrasound and to evaluate the measurement of the ONSAS in relation to age patient and OCT parameters.MethodsThis retrospective study included 53 consecutive eyes of 27 patients with POAG and 64 normal eyes of 32 controls. Both glaucomatous and control groups were divided into 2 subgroups according to age: <60 age (glaucomatous and control group 1) and 61–90 age (glaucomatous and control group 2).ResultsThe ONSAS was significantly lower in all glaucomatous eyes (3.54 ± 0.38) versus normal eyes (3.87 ± 0.32) (p = 0.001). Significant reduction of ONSAS was showed in control group 2 (3.63 mm ± 0.37) compared to control group 1 (3.87 mm ± 0.32) (p = 0.014) and between glaucoma group 1 (3.54 mm ± 0.38) and control group 1 (p = 0.001). While no significant differences were observed between glaucomatous group 2 (3.48 mm ± 0.41) and control group 2 (p = 0.17) and between glaucoma group 1 and glaucoma group 2 (p = 0.609). Lastly, the ONSAS was not significantly associated with GCC and RNFL parameters except for Focal Loss Volume (FLV), Superior RNFL and ONSAS in glaucoma group 1 and for FLV and ONSAS in all glaucomatous group.ConclusionStandardized A-scan ultrasound is a non invasive imaging technique with which it is possible to monitor ONSAS changes in glaucomatous patients. The reduction of ONSAS confirm the importance of the lower orbital CSFP as further risk factor in the progression of glaucoma disease.

Risk factors associated with glaucoma disease progression

Background: Glaucoma is a disease which damage the eye’s optic nerve. That so many instances of glaucoma can be undiscovered ways that research studies based in hospitals or specialist clinics, as an example, can be biased to specific classes of referred patients and so not representative of the Glaucoma associate. Objective: In this review we discuss risk factors that lead to onset of glaucoma and focus on risk factors affecting the progression of this disease, to give information to prevent and start early treatment. Method: PubMed and Embase database were searched up to July, 2018 for relevant studies that discussing the risk factors of glaucoma. Conclusion: The most consistent factors are older age and also higher baseline IOP. Currently, there is very little we can do about age, due to the fact that it is probably a surrogate threat factor for various other potentially more important elements, for example, mitochondrial performance. Because IOP can be lowered either medically or operatively, it is a flexible threat or prognostic element for open-angle glaucoma.

Is glaucoma suitable for community screening

Glaucoma is the leading cause of irreversible blindness worldwide.Screening for glaucoma is a critical intervention to identify individuals at an earlier stage of the disease.However, there is controversy about the necessity of glaucoma screening.Screening is a critical intervention for primary prevention of disease.The screening which suited to the level of our economic development has important benefits for our country, society, families and individuals.Glaucoma has fulfils the criteria of WHO for population screening: (1)Glaucoma is a major public health problem in the world.(2)Glaucoma can be detected in its earlier stage.(3)There are suitable and acceptable examinations for glaucoma screening.(4)Early detection and subsequent treatment could delay or retard glaucoma disease progression.(5)With appropriate strategy design, glaucoma screening can creat good economic benefit.The screening strategies depend on the level of social economy development, the health policies of developed areas tend to prevent disease in its early stages.In poor areas, the limited medical resources are used to treat patients in the advanced stages.In the relatively developed area with complete health care facilities and incomplete referral mechanisms, screening for glaucoma is a critical intervention to identify individuals at an earlier stage of the disease.Glaucoma Screening project in Wenzhou suggested that screening should be implement in relatively developed regions of high density of population to improve efficiency; screening should aim for multiple eye diseases to lower the cost per unit benefit. Key words: Glaucoma; Screening; Necessity

Glaucomatous cell derived matrices differentially modulate non-glaucomatous trabecular meshwork cellular behavior

Ocular hypertension is a causal risk-factor to developing glaucoma. This is associated with stiffening of the trabecular meshwork (TM), the primary site of resistance to aqueous-humor-outflow. The mechanisms underlying this stiffening or how pathologic extracellular matrix (ECM) affects cell function are poorly understood. It is recognized that mechanotransduction systems allow cells to sense and translate the intrinsic biophysical properties of ECM into intracellular signals to control gene transcription, protein expression, and cell behavior. Using an anterior segment perfusion model, we document that there are significantly more low flow regions that are much stiffer, and fewer high flow regions that are less stiff in glaucomatous TM (GTM) when compared to non-glaucomatous TMs (NTM). GTM tissue also has fewer cells overall when compared with NTM tissue. In order to study the role of pathologic ECM in glaucoma disease progression, we conducted studies using cell derived matrices (CDM). First, we characterized the mechanics, composition and organization of fibronectin in ECM deposited by GTM and NTM cells treated with glucocorticosteroids. Then, we determined that these GTM-derived ECM are able to induce stiffening of normal NTM cells, and alter their gene/protein expression to resemble that of a glaucomatous phenotype. Further, we demonstrate that GTM-derived ECM causes endoplasmic reticular stress in NTM. They also became resistant to being reorganized by these NTM cells. These phenomena were exacerbated by ECMs obtained from steroid treated glaucoma model groups. Collectively, our data demonstrates that CDMs represent a novel tool for the study of bidirectional interactions between TM cells and their immediate microenvironment. Statement of SignificanceExtracellular matrix (ECM) changes are prevalent in a number of diseases. The precise mechanisms by which changes in the ECM contribute to disease progression is unclear, primarily due to absence of appropriate models. Here, using glaucoma as a disease model, we document changes in cell derived matrix (CDM) and tissue mechanics that contribute to the pathology. Subsequently, we determine the effect that ECMs from diseased and healthy individuals have on healthy cell behaviors. Data emanating from this study demonstrate that CDMs are a potent tool for the study of cell-ECM interactions.

Combining optical coherence tomography with visual field data to rapidly detect disease progression in glaucoma: a diagnostic accuracy study.

Progressive optic nerve damage in glaucoma results in vision loss, quantifiable with visual field (VF) testing. VF measurements are, however, highly variable, making identification of worsening vision ('progression') challenging. Glaucomatous optic nerve damage can also be measured with imaging techniques such as optical coherence tomography (OCT). To compare statistical methods that combine VF and OCT data with VF-only methods to establish whether or not these allow (1) more rapid identification of glaucoma progression and (2) shorter or smaller clinical trials. Method 'hit rate' (related to sensitivity) was evaluated in subsets of the United Kingdom Glaucoma Treatment Study (UKGTS) and specificity was evaluated in 72 stable glaucoma patients who had 11 VF and OCT tests within 3 months (the RAPID data set). The reference progression detection method was based on Guided Progression Analysis™ (GPA) Software (Carl Zeiss Meditec Inc., Dublin, CA, USA). Index methods were based on previously described approaches [Analysis with Non-Stationary Weibull Error Regression and Spatial enhancement (ANSWERS), Permutation analyses Of Pointwise Linear Regression (PoPLR) and structure-guided ANSWERS (sANSWERS)] or newly developed methods based on Permutation Test (PERM), multivariate hierarchical models with multiple imputation for censored values (MaHMIC) and multivariate generalised estimating equations with multiple imputation for censored values (MaGIC). Ten university and general ophthalmology units (UKGTS) and a single university ophthalmology unit (RAPID). UKGTS participants were newly diagnosed glaucoma patients randomised to intraocular pressure-lowering drops or placebo. RAPID participants had glaucomatous VF loss, were on treatment and were clinically stable. 24-2 VF tests with the Humphrey Field Analyzer and optic nerve imaging with time-domain (TD) Stratus OCT™ (Carl Zeiss Meditec Inc., Dublin, CA, USA). Criterion hit rate and specificity, time to progression, future VF prediction error, proportion progressing in UKGTS treatment groups, hazard ratios (HRs) and study sample size. Criterion specificity was 95% for all tests; the hit rate was 22.2% for GPA, 41.6% for PoPLR, 53.8% for ANSWERS and 61.3% for sANSWERS (all comparisons p ≤ 0.042). Mean survival time (weeks) was 93.6 for GPA, 82.5 for PoPLR, 72.0 for ANSWERS and 69.1 for sANSWERS. The median prediction errors (decibels) when the initial trend was used to predict the final VF were 3.8 (5th to 95th percentile 1.7 to 7.6) for PoPLR, 3.0 (5th to 95th percentile 1.5 to 5.7) for ANSWERS and 2.3 (5th to 95th percentile 1.3 to 4.5) for sANSWERS. HRs were 0.57 [95% confidence interval (CI) 0.34 to 0.90; p = 0.016] for GPA, 0.59 (95% CI 0.42 to 0.83; p = 0.002) for PoPLR, 0.76 (95% CI 0.56 to 1.02; p = 0.065) for ANSWERS and 0.70 (95% CI 0.53 to 0.93; p = 0.012) for sANSWERS. Sample size estimates were not reduced using methods including OCT data. PERM hit rates were between 8.3% and 17.4%. Treatment effects were non-significant in MaHMIC and MaGIC analyses; statistical significance was altered little by incorporating imaging. TD OCT is less precise than current imaging technology; current OCT technology would likely perform better. The size of the RAPID data set limited the precision of criterion specificity estimates. The sANSWERS method combining VF and OCT data had a higher hit rate and identified progression more quickly than the reference and other VF-only methods, and produced more accurate estimates of the progression rate, but did not increase treatment effect statistical significance. Similar studies with current OCT technology need to be undertaken and the statistical methods need refinement. Current Controlled Trials ISRCTN96423140. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 4. See the NIHR Journals Library website for further project information. Data analysed in the study were from the UKGTS. Funding for the UKGTS was provided through an unrestricted investigator-initiated research grant from Pfizer Inc. (New York, NY, USA), with supplementary funding from the NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK. Imaging equipment loans were made by Heidelberg Engineering, Carl Zeiss Meditec and Optovue (Fremont, CA, USA). Pfizer, Heidelberg Engineering, Carl Zeiss Meditec and Optovue had no input into the design, conduct, analysis or reporting of any of the UKGTS findings or this work. The sponsor for both the UKGTS and RAPID data collection was Moorfields Eye Hospital NHS Foundation Trust. David F Garway-Heath, Tuan-Anh Ho and Haogang Zhu are partly funded by the NIHR Biomedical Research Centre based at Moorfields Eye Hospital and UCL Institute of Ophthalmology. David F Garway-Heath's chair at University College London (UCL) is supported by funding from the International Glaucoma Association.

Risk Factors for Rapid Glaucoma Disease Progression

To determine the intraocular and systemic risk factor differences between a cohort of rapid glaucoma disease progressors and nonrapid disease progressors. Retrospective case-control study. Setting: Five private ophthalmology clinics. Forty-eight rapidly progressing eyes (progression ≥1 dB mean deviation [MD]/year) and 486 non-rapidly progressing eyes (progression <1 dB MD/year). Patients were eligible if they had a diagnosis of glaucoma from their ophthalmologist and if they had greater than or equal to 5 Humphrey visual fields (24-2) conducted. Patients were excluded if their sequential visual fields showed an improvement in MD or if they had greater than 5 dB MD variation in between visits. Patients with obvious neurologic fields were excluded. Clinical and demographic data (age, sex, central corneal thickness [CCT], intraocular pressure [IOP], refraction, medications), as well as medical, surgical, and ocular histories, were collected. Risk factor differences between the cohorts were measured using the independent t test, Wald χ2, and binomial regression analysis. Rapid progressors were older, had significantly lower CCT and baseline IOPs, and were more likely to have pseudoexfoliation, disc haemorrhages, ocular medication changes, and IOP-lowering surgery. They also had significantly higher rates of cardiovascular disease and hypotension. Subjects with cardiovascular disease were 2.33 times more likely to develop rapidly progressive glaucoma disease despite significantly lower mean and baseline IOPs. Cardiovascular disease is an important risk factor for rapid glaucoma disease progression irrespective of IOP control.

SURVEY ON A HYBRID APPROACH OF DETECTION OF GLAUCOMA USING SDC BASED METHOD AND LBP FEATURES

Glaucoma is an extreme eye illness that prompts visual deficiency by expansion in weight at the dividers of the front eye. The glaucoma screening has become a research point in the field of biomedical image processing. The glaucoma detection is very essential factor in preventing the loss of eye sight. At the present day glaucoma screening done for 2D retinal fundus images. This paper addresses the survey on the method called “Container to glass” ratio which is very reliable in detecting the status of the progression of glaucoma disease. It classifies the input image into categories of the disease like normal, moderate and medium based on the computed value of the CGR. The CGR is characterized as the proportion of vertical container distance across to the vertical plate breadth. For control of CGR past calculations like territory of the circle, plate location, extraction of container and the extraction of circle must be finished. Consequently glaucoma screening by container to plate proportion will be extremely proficient technique for screening in vast populace based frameworks. Self assessed disk segmentation is the methodology which consolidates the superpixel division, edge recognition and round hough change. Superpixel era is done utilizing SLIC calculation that makes collection of pixel to frame a superpixel. Edge location is essential element for the identification of the region of container and the plate in the division process. Round about hough change which is an element extraction system used to distinguish the state of the sporadic data picture. From these information we can register glass to circle proportion that is the proportion of vertical container to the vertical plate. It will classify the input image into normal, medium and severe cases. This will be very helpful for the patients to know that in which stage the disease is progressed and they can take some preventive measure against vision loss.

Calcium channel blockade reduces mechanical strain-induced extracellular matrix gene response in lamina cribrosa cells

PurposeThis study examines the effect of the L-type calcium channel blocker verapamil on mechanical strain-induced extracellular matrix genes in optic nerve head lamina cribrosa (LC) cells.MethodsChanges in LC cell intracellular...

MMPs in the Neuroretina and Optic Nerve: Modulators of Glaucoma Pathogenesis and Repair?

Multiple studies in glaucoma patients and in animal models of spontaneous and experimentally-induced glaucoma, reported changes in the expression and activity of several matrix metalloproteinases (MMPs) in the retina, optic nerve, aqueous humor, and trabecular meshwork. These data have led to the hypothesis that MMPs might be involved in glaucoma onset and/or disease progression. However, reports are conflicting and research aiming at providing a clear definition of their causative role is lacking. In glaucoma, MMPs are thought to act at two different levels. In the trabecular meshwork, they fine-tune the aqueous humor outflow rate and intraocular pressure, in the neuroretina and optic nerve, however, their role during glaucoma disease progression is much less clear. This review provides a comprehensive overview of the research conducted on the expression and function of MMPs in the retina and optic nerve, and on the elucidation of their potential involvement during glaucoma pathogenesis. Additionally, we describe the insecure balance between detrimental and potential beneficial MMP activities during central nervous system recovery and how MMP-based therapies could help to overcome the current pitfalls in the development of retinal ganglion cell neuroprotection and axon regeneration approaches for the treatment of glaucoma.

Changes in the Visual Cortex in Patients with High-Tension Glaucoma

Objective: To verify whether there is a correlation between visual field changes in high-tension glaucoma and changes in functional magnetic resonance of the visual cortex.Methods and patients: The authors examined nine patients with high-tension glaucoma in different stages by functional magnetic resonance (fMRI). The measurements were carried out on the Philips Achieva 3T TX MR system using the BOLD method. Optical stimulation was provided by a black and white checkerboard alternated with its negative image with a frequency of 2 Hz. Each measurement consisted of a sequence of five 30-second active phase periods and five resting periods of the same length. The obtained data were processed using SPM8 software.The complex ophthalmological examination was supplemented by the visual field in the rapid threshold program mode. The sum of sensitivities in the homolateral halves of the visual fields (ranging from 0-22 degrees) was compared to the extent of fMRI contralateral activity of the visual cortex. The group was compared to a group of eight healthy persons.Results: The obtained data were subjected to a statistical analysis (Non-parametric Spearman’s rank correlation coefficient) which showed a medium-grade correlation between the visual field changes and the changes in the visual cortex. R=0.667 (p<0.05), R=0.767 (p< 0.016) respectively.Conclusion: The authors proved that the progression of glaucoma disease corresponds to the functional changes in the cerebral cortex. The loss of ganglion cells of the striate cortex most probably results in the interconnection of the optical radiation with the functional ganglion cells of the temporal lobe.