Glaucoma-related Changes Research Articles

Comparison of retinal nerve fiber thickness in emmetropes, myopes and hyperopes using optical coherence tomography

Aim of this study was to analyze retinal nerve fiber layer thickness by using spectral domen Optical Coherence Tomography (OCT) in different refractive status (emmetrops, myopes and hypermetrops).A cross-sectional study involved 150 patients aged 18-40, with and without refractive errors. Three groups (Emmetropic, Myopic, Hypermetropic) were tested using spectral domain OCT after pupil dilation, comparing RNFL thickness.In this study, 150 participants were categorized into three groups: emmetropia, myopia, and hypermetropia. The age group most represented was 21-25 years, comprising 35.3% of the sample. Of the total, 80 were male (53.3%), and 70 were female. Among males, 22 patients were emmetropia, myopia in 31 and hypermetropia in 27. The mean axial length for emmetropia was 23.54 ± 0.48 SD, myopia was 24.53 ± 0.48 and hypermetropia was 22.36 ± 1.11. Hypermetropia was further categorized into low-grade 22.49 ± 1.06 SD, moderate 22.26 ± 1.12 SD and high-grade 22.45 ± 1.00 based on axial length.Myopic individuals exhibited significant RNFL thinning, particularly in the inferior and superior quadrants, resembling early glaucoma-related changes. This has implications for glaucoma suspect evaluations.

Association Analysis between Cognitive Function Score and Inner Macular Thickness/Visual Field Sensitivity in Glaucoma Patients.

(1) Background: Previous research has investigated the relationship between cognitive impairment, optical coherence tomography (OCT), visual fields (VF), and VF reliability in smaller patient samples using various cognitive assessment tools. This study analyzed the relationship between cognitive function scores using the Mini-Cog test and inner macular thickness (IMT) and VF sensitivity in glaucoma patients. (2) Methods: A retrospective analysis was conducted on 984 patients with 1897 eyes. Assessments included age, sex, intraocular pressure (IOP), and Mini-Cog test scores. Abnormal Mini-Cog scores were observed in 89 patients (9%). Using a mixed-effects model adjusted for background factors, the association between Mini-Cog scores and IMT, parafoveal (PF)-IMT, mean deviation (MD), pattern standard deviation, fixation losses (FL), false negatives (FN), and false positives (FP) was analyzed. (3) Results: Abnormal Mini-Cog scores (≤2) were associated with thinning of the IMT and PF-IMT, worse MDs, and higher FN and FP rates but not with PSD or FL. (4) Conclusions: Glaucoma patients with low cognitive function scores exhibited more advanced glaucoma-related changes in VF testing and morphological tests. Further longitudinal studies are needed to explore the relationship between glaucoma and cognitive impairment.

Altered Resting-State Amygdalar Functional Connectivity in Primary Angle-Closure Glaucoma Patients.

Glaucoma patients frequently present with depressive symptoms, the development of which is closely associated with amygdalar activity. However, no studies to date have documented glaucoma-related changes in the functional connectivity (FC) of the amygdala. Accordingly, resting-state functional magnetic resonance imaging (rs-fMRI) analyses were herein used to evaluate changes in amygdalar FC in primary angle-closure glaucoma (PACG) patients. In total, this study enrolled 36 PACG patients and 33 healthy controls (HCs). Complete eye exams were conducted for all PACG patients. After the preprocessing of magnetic resonance imaging (MRI) data, the bilateral amygdala was selected as a seed point, followed by the comparison of resting-state FC between the PACG and HC groups. Then, those brain regions exhibiting significant differences between these groups were identified, and relationships between the FC coefficient values for these regions and clinical variables of interest were assessed. These analyses revealed that as compared to HC individuals, PACG patients exhibited reductions in FC between the amygdala and the cerebellum_8, vermis_4_5, anterior central gyrus, supplementary motor area, paracentral lobule, putamen, middle frontal gyrus, and posterior cingulate gyrus, while enhanced FC was detected between the right and left amygdala. No significant correlations between these changes in amygdalar any any disease-related clinical parameters or disease duration were noted. Patients with PACG exhibit extensive resting state abnormalities with respect to the FC between the amygdala and other regions of the brain, suggesting that dysregulated amygdalar FC may play a role in the pathophysiology of PACG.

Sensitivity and specificity of the uniform field electroretinogram in glaucoma detection in comparison to the pattern electroretinogram.

To determine the ability of the photopic negative response (PhNR) of the uniform field electroretinogram (UF-ERG) to identify early glaucomatous changes in comparison to the checkerboard and bar stimuli of the pattern electroretinogram (PERG). Forty-nine glaucoma patients were classified into two groups: glaucoma-suspect (23 eyes) and early to moderate glaucoma (30 eyes), based on their clinical examination and the results of standard automated perimetry. Thirty patients (30 eyes) with intraocular pressures (IOP) of 21mmHg or less, with no history of reported high IOP, were included as controls. PERG and UF-ERG recordings were obtained on a Diagnosys D-341 Attaché-Envoy System. Visual field testing was done only for glaucoma-suspect and glaucoma patients. All three tests (PERG bar stimulus, PERG checkerboard stimulus and PhNR) displayed significantly prolonged peak times for glaucoma and glaucoma-suspect patients, with delays ranging from 7.8 to 14.8%, depending on the test. The PERG bar stimulus also showed a significantly lower N95 amplitude for both glaucoma groups (with reductions of 26.0% and 33.0% for glaucoma-suspect and glaucoma groups, respectively). The PERG checkerboard N95 amplitude component had high sensitivity for detecting glaucoma patients but a low specificity (97% and 37%, respectively; AUC = 0.61). Overall, the PhNR peak time showed the highest sensitivity and specificity (77% and 90%, respectively; AUC = 0.87). PERG bar stimuli and the PhNR of the UF-ERG can be used in the clinical setting to detect glaucoma-related changes in glaucoma-suspect and glaucoma patients. However, our data confirm that the PhNR peak time has the best combined sensitivity and specificity.

Efficacy, Drug Sensitivity, and Safety of a Chronic Ocular Hypertension Rat Model Established Using a Single Intracameral Injection of Hydrogel into the Anterior Chamber.

BackgroundChronic ocular hypertension (COH) models mostly focus on changes in intraocular pressure (IOP) and loss of retinal ganglion cells (RGCs). The present study evaluated important glaucoma-related changes in visual function, response to common ocular hypotensive drugs, and safety for our previously developed rat model.Material/MethodsThe model was established through a single injection of hydrogel into the anterior chambers. Efficacy was assessed through F-VEP by measuring latency and amplitude of P1. We evenly divided 112 rats into 4 groups: control and COH at 2, 4, and 8 weeks. Response to 5 common drugs (brimonidine, timolol, benzamide, pilocarpine, and bimatoprost) were each tested on 6 rats and assessed using difference in IOP. Safety assessment was conducted through histological analysis of 24 rats evenly divided into 4 groups of control and COH at 2, 4, and 8 weeks. Corneal endothelial cells (CECs) of 24 additional rats were used to determine toxic effects through TUNEL and CCK-8 assays.ResultsP1 latency and amplitude of VEP demonstrated the model is effective in inducing optic nerve function impairment. Only the drug pilocarpine failed to have an obvious hypotensive effect, while the other 4 were effective. CECs at 2, 4, and 8 weeks showed no significant differences from control groups in results of histological analysis, TUNEL, and CCK-8 assays.ConclusionsA single injection of hydrogel into the anterior chamber is effective for modeling COH, can respond to most commonly used hypotensive drugs, and is non-toxic to the eyes.

Glaucoma-related central visual field deterioration after vitrectomy for epiretinal membrane: topographic characteristics and risk factors.

To identify risk factors for glaucoma-related central visual field (VF) deterioration after vitrectomy with internal limiting membrane (ILM) peeling for epiretinal membrane (ERM). A prospective cohort study consisting of cases with or without glaucoma (33 eyes of 33 patients in each group) who underwent vitrectomy with ILM peeling for ERM. Humphrey 10-2 VFs and ganglion cell complex (GCC) thickness were measured at baseline and about 3, 6, and 12 months postoperatively. Longitudinal changes in VF indices and factors associated with their postoperative changes were investigated using mixed-effects models, as was sectorwise total deviation (TD) analysis using six sectors consisting of outer/inner arcuate and cecocentral sectors in each hemifield. VF mean deviation significantly deteriorated postoperatively only in the glaucoma group (P < 0.001). Older age, longer axial length, preoperative worse mean deviation, and thinner GCC were significant risk factors for postoperative deterioration (coefficient ± standard errors: -0.139 ± 0.067, -0.740 ± 0.241, 0.16 ± 0.07, 0.050 ± 0.020; P = 0.038, P = 0.002, P = 0.024, P = 0.012, respectively). Sectorwise analysis revealed that TD in the superior/inferior outer arcuate sectors significantly deteriorated only in the glaucoma group. Preoperative worse TD and thinner GCC were significant risk factors for deterioration in the superior outer arcuate sector (0.65 ± 0.11, 0.08 ± 0.03; P < 0.001, P = 0.042, respectively). Central VF deterioration, especially in the outer arcuate sectors, found to be glaucoma-related changes after vitrectomy with ILM peeling for ERM. Preoperative worse VF and thinner GCC were identified as risk factors for postoperative VF deterioration.

Expansion of retinal nerve fiber bundle narrowing in glaucoma: An adaptive optics scanning laser ophthalmoscopy study

PurposeTo investigate longitudinal changes in the retinal nerve fiber bundle in eyes with primary open angle glaucoma using adaptive optics scanning laser ophthalmoscopy. MethodsA prospective observational case series. Fourteen eyes from 12 patients with primary open angle glaucoma that exhibited retinal nerve fiber layer defects on fundus photography were imaged with adaptive optics scanning laser ophthalmoscopy over time. ResultsThe expansion of retinal nerve fiber bundle narrowing was observed on adaptive optics scanning laser ophthalmoscopy in 8 eyes (57.1%) over a period of 1.44 ± 0.42 years. Retinal nerve fiber bundle narrowing expanded horizontally in 2 eyes and vertically in 6 eyes. In 3 eyes, changes in the retinal nerve fiber layer were only detectable on adaptive optics scanning laser ophthalmoscopy images. Conclusions and ImportanceThe expansion of retinal nerve fiber bundle narrowing was observed using adaptive optics scanning laser ophthalmoscopy. Accordingly, this tool may be a useful tool for detecting glaucoma-related changes in retinal nerve fibers in a short time.

Glaucoma-Related Differences in Gaze Behavior When Negotiating Obstacles.

PurposeSafe navigation requires avoiding objects. Visual field loss may affect how one visually samples the environment, and may thus contribute to bumping into objects and falls. We tested the hypothesis that gaze strategies and the number of collisions differ between people with glaucoma and normally sighted controls when navigating around obstacles, particularly under multitasking situations.MethodsTwenty persons with moderate–severe glaucoma and 20 normally sighted controls walked around a series of irregularly spaced vertical obstacles under the following three conditions: walking with obstacles only, walking and counting backward to simulate a conversation, and walking while performing a concurrent visual search task to simulate locating a landmark. We quantified gaze patterns and the number of obstacle contacts.ResultsCompared with controls, people with glaucoma directed gaze closer to their current position (P < 0.05). They also directed a larger proportion of fixations (in terms of number and duration) to obstacles (P < 0.05). Despite this finding, considerably more people with glaucoma contacted an obstacle (P < 0.05). Multitasking led to changes in gaze behavior in both groups, and this was accompanied by a large increase in obstacle contacts among those with glaucoma (P < 0.05).ConclusionsGlaucoma alters gaze patterns when negotiating a series of obstacles and increases the likelihood of collisions. Multitasking in this situation exacerbates these changes.Translational RelevanceUnderstanding glaucoma-related changes in gaze behavior during walking in cluttered environments may provide critical insight for orientation and mobility specialists and guide the design of gaze training interventions to improve mobility.

Glaucoma-related changes in gaze behavior affect mobility but are modifiable

Glaucoma-related changes in gaze behavior affect mobility but are modifiable

Losartan Treatment Protects Retinal Ganglion Cells and Alters Scleral Remodeling in Experimental Glaucoma.

PurposeTo determine if oral losartan treatment decreases the retinal ganglion cell (RGC) death caused by experimental intraocular pressure (IOP) elevation in mice.MethodsWe produced IOP increase in CD1 mice and performed unilateral optic nerve crush. Mice received oral losartan, spironolactone, enalapril, or no drug to test effects of inhibiting angiotensin receptors. IOP was monitored by Tonolab, and blood pressure was monitored by tail cuff device. RGC loss was measured in masked axon counts and RGC bodies by β-tubulin labeling. Scleral changes that could modulate RGC injury were measured including axial length, scleral thickness, and retinal layer thicknesses, pressure-strain behavior in inflation testing, and study of angiotensin receptors and pathways by reverse transcription polymerase chain reaction, Western blot, and immunohistochemistry.ResultsLosartan treatment prevented significant RGC loss (median loss = 2.5%, p = 0.13), while median loss with water, spironolactone, and enalapril treatments were 26%, 28% and 43%; p < 0.0001). The lower RGC loss with losartan was significantly less than the loss with spironolactone or enalapril (regression model p = 0.001; drug treatment group term p = 0.01). Both losartan and enalapril significantly lowered blood pressure (p< 0.001), but losartan was protective, while enalapril led to worse than water-treated RGC loss. RGC loss after crush injury was unaffected by losartan treatment (difference from control p = 0.9). Survival of RGC in cell culture was not prolonged by sartan treatment. Axonal transport blockade after 3 day IOP elevations was less in losartan-treated than in control glaucoma eyes (p = 0.007). Losartan inhibited effects of glaucoma, including reduction in extracellular signal-related kinase activity and modification of glaucoma-related changes in scleral thickness and creep under controlled IOP.ConclusionsThe neuroprotective effect of losartan in mouse glaucoma is associated with adaptive changes in the sclera expressed at the optic nerve head.

Corneal deformation dynamics in normal and glaucoma patients utilizing scheimpflug imaging.

The purpose of this study was to explore the corneal deformation dynamics recorded in raw Scheimpflug images of CorVis ST tonometer to evaluate age- and glaucoma-related changes in corneal biomechanics. This was a prospective study in which 18 subjects were recruited and divided into three equal groups (healthy young, healthy older and older glaucoma group). Up to three measurements by CorVis ST tonometer were acquired on the left eye of each subject. Raw Scheimpflug images of CorVis ST were used to extract changes in anterior and posterior corneal profiles, which were further modeled by a Chebyshev polynomial expansion of optimally determined order. Corneal deformation dynamics were studied via time-varying series of Chebyshev polynomial coefficients, in which three phases of corneal deformation were determined. The first and the last phase of corneal dynamics were fitted with bilinear functions. Further, the slope of each linear trend in the model was tested between the groups. Statistically significant differences were observed in the final return phase of corneal dynamics between the older group of subjects and those of glaucoma subjects indicating possible biomechanical differences in their tissues that could only be observed with minimum applied pressure.

Glaucoma-related Changes in the Mechanical Properties and Collagen Micro-architecture of the Human Sclera.

ObjectiveThe biomechanical behavior of the sclera determines the level of mechanical insult from intraocular pressure to the axons and tissues of the optic nerve head, as is of interest in glaucoma. In this study, we measure the collagen fiber structure and the strain response, and estimate the material properties of glaucomatous and normal human donor scleras.MethodsTwenty-two posterior scleras from normal and diagnosed glaucoma donors were obtained from an eyebank. Optic nerve cross-sections were graded to determine the presence of axon loss. The specimens were subjected to pressure-controlled inflation testing. Full-field displacement maps were measured by digital image correlation (DIC) and spatially differentiated to compute surface strains. Maps of the collagen fiber structure across the posterior sclera of each inflated specimen were obtained using synchrotron wide-angle X-ray scattering (WAXS). Finite element (FE) models of the posterior scleras, incorporating a specimen-specific representation of the collagen structure, were constructed from the DIC-measured geometry. An inverse finite element analysis was developed to estimate the stiffness of the collagen fiber and inter-fiber matrix.ResultsThe differences between glaucoma and non-glaucoma eyes were small in magnitude. Sectorial variations of degree of fiber alignment and peripapillary scleral strain significantly differed between normal and diagnosed glaucoma specimens. Meridional strains were on average larger in diagnosed glaucoma eyes compared with normal specimens. Non-glaucoma specimens had on average the lowest matrix and fiber stiffness, followed by undamaged glaucoma eyes, and damaged glaucoma eyes but the differences in stiffness were not significant.ConclusionThe observed biomechanical and microstructural changes could be the result of tissue remodeling occuring in glaucoma and are likely to alter the mechanical environment of the optic nerve head and contribute to axonal damage.

Stressor-dependent Alterations in Glycoprotein 130: Implications for Glial Cell Reactivity, Cytokine Signaling and Ganglion Cell Health in Glaucoma.

The interleukin-6 (IL-6) family of cytokines is associated with retinal ganglion cell (RGC) survival and glial reactivity in glaucoma. The purpose of this study was to evaluate glaucoma-related changes in glycoprotein-130 (gp130), the common signal transducer of the IL-6 family of cytokines, as they relate to RGC health, glial reactivity and expression of IL-6 cytokine family members. For all experiments, we examined healthy retina (young C57), aged retina (aged C57), retina predisposed to glaucoma (young DBA/2) and retina with IOP-induced glaucoma (aged DBA/2). We determined retinal gene expression of gp130 and IL-6 family members, using quantitative PCR, and protein expression of gp130, using multiplex ELISA. For protein localization and cell-specific expression, we performed co-immunolabeling for gp130 and cell type-specific markers. We used quantitative microscopy to measure layer-specific expression of gp130 and its relationships to astrocyte and Müller glia reactivity and RGC axonal transport, as determined by uptake and transport of cholera toxin β-subunit (CTB). Gene expression of gp130 was elevated with all glaucoma-related stressors, but only normal aging increased protein levels. In healthy retina, gp130 localized primarily to the inner retina, where it was expressed by astrocytes, Müller cells and RGCs. Layer-specific analysis of gp130 expression revealed increased expression in aging retina and decreased expression in glaucomatous retina that was eccentricity-dependent. These glaucoma-related changes in gp130 expression correlated with the level of GFAP and glutamine synthetase expression, as well as axonal transport in RGCs. The relationships between gp130, glial reactivity and RGC health could impact signaling by many IL-6 family cytokines, which exhibited overall increased expression in a stressor-dependent manner. Glaucoma-related stressors, including normal aging, glaucoma predisposition and IOP-induced glaucoma, differentially alter expression of gp130 and these alterations have direct implications for astrocyte and Müller glia reactivity, RGC health and cytokine signaling.

Biomechanics of the Human Posterior Sclera: Age- and Glaucoma-Related Changes Measured Using Inflation Testing

The objective of this study was to measure the biomechanical response of the human posterior sclera in vitro and to estimate the effects of age and glaucoma. Scleral specimens from 22 donors with no history of glaucoma and 11 donors with a history of glaucoma were excised 3 mm posterior to the equator and affixed to an inflation chamber. Optic nerve cross-sections were graded to determine the presence of axon loss. The time-dependent inflation response was measured in a series of pressure-controlled load-unload tests to 30 mm Hg and creep tests to 15 and 30 mm Hg. Circumferential and meridional strains were computed from the digital image correlation displacements, and midposterior stresses were determined from pressure and deformed geometry. Among normal specimens, older age was predictive of a stiffer response and a thinner sclera. In the age group 75 to 93, diagnosed glaucoma eyes with axon damage were thicker than normal eyes. Both damaged and undamaged glaucoma eyes had a different strain response in the peripapillary sclera characterized by a stiffer meridional response. Undamaged glaucoma eyes had slower circumferential creep rates in the peripapillary sclera than normal eyes. Glaucoma eyes were not different from normal eyes in stresses and strains in the midposterior sclera. The observed differences in the biomechanical response of normal and glaucoma sclera may represent baseline properties that contribute to axon damage, or may be characteristics that result from glaucomatous disease.

Changes in aqueous humor dynamics with age and glaucoma

Changes in aqueous humor dynamics with age and in glaucoma have been studied for several decades. More recently, techniques have been developed which confirm earlier studies showing that outflow facility decreases with age and in glaucoma and add the newer finding that uveoscleral outflow also decreases. Morphologic studies in aging and glaucoma eyes have shown an increase in accumulation of extracellular material in both the trabecular meshwork and ciliary muscle and a loss of trabecular meshwork cells, which contribute to this reduction in outflow and result in an increase in intraocular pressure. A reduction in hyaluronic acid and increases in fibronectin and thrombospondin contribute to the change in the extracellular environment. Imbalances in responses to age-related stresses such as oxidative damage to long-lived molecules, protein cross-linking and loss of elasticity could trigger excess production of factors such as transforming growth factor beta, interleukin-1 and CD44S that could stimulate pathways leading to increases in fibronectin, transformation of trabecular meshwork cells to a myoepithelial state and decrease the breakdown in extracellular matrix material, allowing excess to accumulate. Ultimately trabecular outflow and uveoscleral outflow are reduced and intraocular pressure becomes elevated, adding more stress and perpetuating the pathological condition. Future research to identify additional factors and clarify their roles in these processes could lead to alternative therapies for age and glaucoma related changes in the eye.

Modifications of Visual Evoked Potentials in Patients with Glaucoma

We compared the visual evoked EEG potentials (VEP) elicited by presentation of a reversal chess pattern in patients with glaucoma and in the control group. Amplitudes, peak latencies of the main VEP components (N75, P100, and N145), interpeak intervals, and interpeak magnitudes were measured, and a spectral analysis of the averaged VEP was performed. In patients suffering from glaucoma, the latencies of the N75 and P100 components were greater, while the interpeak intervals P100-N145 and N75-N145 were shorter, than those in the control group. Glaucoma-related changes in the VEP spectral characteristics, in particular a drop in the spectral power of oscillations corresponding to the alpha rhythm, were observed.