Risk Factor For Glaucoma Research Articles

Myopia and Other Refractive Error and Their Relationships to Glaucoma Screening.

A large disk, a large parapapillary delta zone and a long axial length may be used as screening criteria to detect glaucomatous optic neuropathy in highly myopic eyes. To describe aspects for screening of glaucomatous optic neuropathy in dependence of refractive error, under special consideration of high myopia. Studies on the anatomy of the myopic optic nerve head and results of investigations on the relationship between glaucomatous optic neuropathy and axial myopia were included. In the range from hyperopia to moderate myopia, refractive error is not a strong glaucoma risk factor and may not be included in glaucoma screening strategies. Care should be taken, that in moderate myopia, a shift of Bruch´s membrane opening usually into the temporal direction leads to parapapillary gamma zone and a corresponding shortening of the horizontal disk diameter. In these moderately myopic eyes, a secondarily small optic disk with a correspondingly small optic cup should not lead to an overlooking of intrapapillary glaucomatous changes. Prevalence of glaucomatous or glaucoma-like optic nerve atrophy (GOA) steeply increases with longer axial length in highly myopic eyes (cutoff approximately -8 diopters/axial length 26.5mm), with prevalences higher than 50% in extremely high myopia. Besides longer axial length, morphological parameters associated with GOA in highly myopic eyes are a secondarily enlarged disk and large parapapillary delta zone. Both parameters, together with long axial length, may be used as screening criteria in high myopia for GOA. The latter is characterized by an abnormal neuroretinal rim shape, that is, vessel kinking close to the intrapapillary disk border. Factors associated with nonglaucomatous optic neuropathy are larger gamma zone and longer axial length, potentially due to an axial elongation-related retinal nerve fiber stretching.

CRISPR-CasRx-mediated disruption of Aqp1/Adrb2/Rock1/Rock2 genes reduces intraocular pressure and retinal ganglion cell damage in mice

Glaucoma affects approximately 80 million individuals worldwide, a condition for which current treatment options are inadequate. The primary risk factor for glaucoma is elevated intraocular pressure. Intraocular pressure is determined by the balance between the secretion and outflow of aqueous humor. Here we show that using the RNA interference tool CasRx based on shH10 adenovirus-associated virus can reduce the expression of the aqueous humor circulation related genes Rock1 and Rock2, as well as aquaporin 1 and β2 adrenergic receptor in female mice. This significantly reduced intraocular pressure in female mice and provided protection to the retina ganglion cells, ultimately delaying disease progression. In addition, we elucidated the mechanisms by which the knockdown of Rock1 and Rock2, or aquaporin 1 and β2 adrenergic receptor in female mice, reduces the intraocular pressure and secures the retina ganglion cells by single-cell sequencing.

High Intraocular Pressure Is Independently Associated With New-Onset Systemic Hypertension Over a 10-Year Period.

Systemic hypertension (HT) is associated with the development of increased intraocular pressure (IOP), a risk factor for glaucoma. However, it remains unclear whether high IOP is a risk factor for HT.Methods and Results: We investigated 7,487 Japanese individuals (4,714 men, 2,773 women; mean [±SD] age 49±9 years) who underwent annual health checkups in 2006. Over the 10-year follow-up period, 1,232 (24.3%) men and 370 (11.5%) women developed new-onset HT, defined as initiation of antihypertensive drug treatment or blood pressure ≥140/90 mmHg. After dividing IOP into tertiles (T1-T3), Cox proportional hazards analysis (adjusted for age, sex, systolic blood pressure, obesity, current smoking, alcohol consumption, family history of HT, estimated glomerular filtration rate, and diabetes and dyslipidemia diagnoses at baseline) revealed a significantly higher risk of newly developed HT in T3 (IOP ≥14 mmHg; hazard ratio 1.14; 95% confidence interval 1.01-1.29; P=0.038) using T1 (IOP ≤11 mmHg) as the reference group. There was no significant interaction between sex and IOP tertile (P=0.153). A restricted cubic spline model showed a gradual but robust increase in the hazard ratio for new-onset HT with increasing IOP. High IOP is an independent risk factor for the development of HT over a 10-year period.

Current trends and prospects of the local antihypertensive drugs development for the glaucoma treatment

Glaucoma is one of the world’s primary causes of blindness. Russia is following the global increasing trends of glaucoma and its leading position among ophthalmic pathologies that cause irreversible loss of vision. Elevated intraocular pressure (IOP) is the only modifiable risk factor of glaucoma, so treatment strategies specifically focus on reducing IOP by suppressing the production of intraocular fluid and boosting its outflow. The current review presents new medications aimed at glaucoma and high IOP control that have recently appeared at the international market as well as the drugs under the different stages of development, from experimental to clinical studies. These include both the developments of agents belonging to the existing classes and of entirely new drugs intended to control IOP. In an attempt to reduce the side effects of locally administered drugs and prolong their action, in parallel with the development of new drugs, there is also evidence of alternative methods of drug delivery: intraocular implants, injectable forms and obturators, combinations of polymers and colloidal systems.

Liquid-alloy-based dual sensing elements contact lens sensor for continuous intraocular pressure monitoring

Intraocular pressure (IOP) fluctuation is an independent risk factor for glaucoma and a key to clarify its pathogenesis. We have developed a contact lens integrated with a conformal LC resonance circuit made of liquid alloy (Galinstan) for non-invasive continuous IOP monitoring. The contact lens is fabricated using polydimethylsiloxane (PDMS), in which the LC resonance circuit can sense corneal strain proportionally caused by IOP variation. The Galinstan configuration is formed to the designed pattern by UV-laser treating the carbon-doped Ecoflex (c-Ecoflex) stamps and then selectively transferring the Galinstan onto the stamp to form the LC resonance circuit pattern. The tests conducted on silicone model eyes demonstrate high sensitivity in the frequency responses to variations in IOP, reaching 649 ppm/mmHg. IOP measurement on human eyes during head-down tilt bedrest confirms its applicability. With process optimization, this contact lens sensor has great potential for mass production and wide application in monitoring IOP.

Peripheral blood mononuclear cell respiratory function is associated with progressive glaucomatous vision loss

Intraocular pressure (IOP) is currently the only modifiable risk factor for glaucoma and all licensed treatments lower IOP. However, many patients continue to lose vision despite IOP-lowering treatment. Identifying biomarkers for progressive vision loss would have considerable clinical utility. We demonstrate that lower peripheral blood mononuclear cell (PBMC) oxygen consumption rate (OCR) is strongly associated with faster visual field (VF) progression in patients treated by lowering IOP (P < 0.001, 229 eyes of 139 participants), explaining 13% of variance in the rate of progression. In a separate reference cohort of untreated patients with glaucoma (213 eyes of 213 participants), IOP explained 16% of VF progression variance. OCR is lower in patients with glaucoma (n = 168) than in controls (n = 50; P < 0.001) and is lower in patients with low baseline IOP (n = 99) than those with high baseline IOP (n = 69; P < 0.01). PBMC nicotinamide adenine dinucleotide (NAD) levels are lower in patients with glaucoma (n = 29) compared to controls (n = 25; P < 0.001) and strongly associated with OCR (P < 0.001). Our results support PBMC OCR and NAD levels as new biomarkers for progressive glaucoma.

Progressive Paracentral Visual Field Loss at Low Intraocular Pressures Following LASIK.

Intraocular pressure is currently the only known reliable, modifiable risk factor for the development and progression of glaucoma. Other risk factors for glaucoma include increasing age, myopia, decreased central corneal thickness, and low corneal hysteresis (CH) measurements. Photoablative keratorefractive surgery including laser assisted in situ keratomileusis (LASIK) has become a common way to treat refractive error, with over 25 million procedures performed in the United States alone. Though myopic LASIK has been associated with a decrease in CH measurements, relatively little is known about the risk of LASIK on glaucoma onset and progression. Here we present an observational study of 4 consecutive relatively young and otherwise healthy glaucoma patients with a history of myopic LASIK who showed progression of paracentral visual field deficits at intraocular pressures of 12mmHg or less while being carefully monitored. Therefore, these patients required lower targets of intraocular pressure, in the single-digit range, to slow or halt progression. In this cohort, the average corneal hysteresis was more than 2 standard deviations below normal values. This series suggests that additional study into the association of LASIK and glaucoma is warranted, including the potential risk contribution of diminished CH. These studies may be particularly relevant as patients who underwent LASIK procedures in the early 2000s may now be at increased risk of glaucoma due to the risk factor of age.

Remyelination-oriented clemastine treatment attenuates neuropathies of optic nerve and retina in glaucoma.

As one of the top causes of blindness worldwide, glaucoma leads to diverse optic neuropathies such as degeneration of retinal ganglion cells (RGCs). It is widely accepted that the level of intraocular pressure (IOP) is a major risk factor in human glaucoma, and reduction of IOP level is the principally most well-known method to prevent cell death of RGCs. However, clinical studies show that lowering IOP fails to prevent RGC degeneration in the progression of glaucoma. Thus, a comprehensive understanding of glaucoma pathological process is required for developing new therapeutic strategies. In this study, we provide functional and histological evidence showing that optic nerve defects occurred before retina damage in an ocular hypertension glaucoma mouse model, in which oligodendroglial lineage cells were responsible for the subsequent neuropathology. By treatment with clemastine, an Food and Drug Administration (FDA)-approved first-generation antihistamine medicine, we demonstrate that the optic nerve and retina damages were attenuated via promoting oligodendrocyte precursor cell (OPC) differentiation and enhancing remyelination. Taken together, our results reveal the timeline of the optic neuropathies in glaucoma and highlight the potential role of oligodendroglial lineage cells playing in its treatment. Clemastine may be used in future clinical applications for demyelination-associated glaucoma.

Low Macular Pigment Optical Density Is Associated with Manifest Primary Open-Angle Glaucoma in Older Women

BackgroundLower density of carotenoids lutein and zeaxanthin (L/Z) in the macula (i.e., macular pigment) has been linked to greater risk for age-related eye disease. ObjectivesWe evaluated whether macular pigment optical density (MPOD) was associated with manifest primary open-angle glaucoma (POAG) among older women in the Carotenoids in Age-Related Eye Disease Study 2 (CAREDS2). MethodsMPOD was measured with customized heterochromatic flicker photometry in women who attended CAREDS2 (2016–2019) and CAREDS1 (2001–2004) study visits. Manifest POAG at CAREDS2 was assessed using visual fields, disc photos, optical coherence tomography, and medical records. Age-adjusted linear and logistic regression models were used to investigate the cross-sectional association between POAG and MPOD at CAREDS2, and MPOD measured 15 years earlier at CAREDS1. ResultsAmong 426 CAREDS2 participants (mean age: 80 y; range: 69–98 y), 26 eyes with manifest POAG from 26 participants were identified. Glaucomatous eyes had 25% lower MPOD compared to nonglaucomatous eyes [mean (SE): 0.40 (0.05) compared with 0.53 (0.01)] optical density units (ODU), respectively (P = 0.01). Compared with MPOD quartile 1, odds for POAG were lower for women in quartiles 2–4 (P-trend = 0.01). After excluding eyes with age-related macular degeneration, associations were similar but not statistically significant (P-trend = 0.16). Results were similar for MPOD measured at CAREDS1. ConclusionsOur results add to growing evidence that low MPOD may be a novel glaucoma risk factor and support further studies to assess the utility of dietary interventions for glaucoma prevention.

Risk factors for exfoliation glaucoma - Current evidence and perspectives.

Exfoliation syndrome (XFS) and exfoliation glaucoma (XFG) represent a complex matrix of ocular age-related neurodegenerative changes. Numerous decades of research on this disease entity have highlighted the unique clinical features of ocular protein-complex aggregates, which lead to tissue dysfunction of the ocular outflow channels, leading to irreversible optic nerve damage and glaucoma. While genetic studies have reported several genes associated with XFS and XFG, numerous studies have shown their association with common systemic diseases such as ischemic heart disease, cerebrovascular accidents, and hypertension. Environmental factors are also reported to play a role in the disease pathogenesis by epigenetic control of gene expression and partly explain the difference in the prevalence rates of the disease process. Despite the identification of possible triggers for the disease onset or for the development of glaucoma, the exact mechanisms or the role of several reported risk factors in disease pathogenesis remain a mystery. This review comprehensively evaluated the several risk factors in XFS and XFG while discussing the interactive interplay between the risk factors that determine the disease onset or phenotype in XFS and XFG.

The Association of Urinary Sodium Excretion with Glaucoma and Related Traits in a Large United Kingdom Population

Excessive dietary sodium intake has known adverse effects on intravascular fluid volume and systemic blood pressure, which may influence intraocular pressure (IOP) and glaucoma risk. This study aimed to assess the association of urinary sodium excretion, a biomarker of dietary intake, with glaucoma and related traits, and determine whether this relationship is modified by genetic susceptibility to disease. Cross-sectional observational and gene-environment interaction analyses in the population-based UK Biobank study. Up to 103 634 individuals (mean age: 57 years; 51% women) with complete urinary, ocular, and covariable data. Urine sodium:creatinine ratio (UNa:Cr; mmol:mmol) was calculated from a midstream urine sample. Ocular parameters were measured as part of a comprehensive eye examination, and glaucoma case ascertainment was through a combination of self-report and linked national hospital records. Genetic susceptibility to glaucoma was calculated based on a glaucoma polygenic risk score comprising 2673 common genetic variants. Multivariable linear and logistic regression, adjusted for key sociodemographic, medical, anthropometric, and lifestyle factors, were used to model associations and gene-environment interactions. Corneal-compensated IOP, OCT derived macular retinal nerve fiber layer and ganglion cell-inner plexiform layer (GCIPL) thickness, and prevalent glaucoma. In maximally adjusted regression models, a 1 standard deviation increase in UNa:Cr was associated with higher IOP (0.14 mmHg; 95% confidence interval [CI], 0.12-0.17; P<0.001) and greater prevalence of glaucoma (odds ratio, 1.11; 95% CI, 1.07-1.14; P<0.001) but not macular retinal nerve fiber layer or ganglion cell-inner plexiform layer thickness. Compared with those with UNa:Cr in the lowest quintile, those in the highest quintile had significantly higher IOP (0.45 mmHg; 95% CI, 0.36-0.53, P<0.001) and prevalence of glaucoma (odds ratio, 1.30; 95% CI, 1.17-1.45; P<0.001). Stronger associations with glaucoma (P interaction=0.001) were noted in participants with a higher glaucoma polygenic risk score. Urinary sodium excretion, a biomarker of dietary intake, may represent an important modifiable risk factor for glaucoma, especially in individuals at high underlying genetic risk. These findings warrant further investigation because they may have important clinical and public health implications. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

POU6F2, a risk factor for glaucoma, myopia and dyslexia, labels specific populations of retinal ganglion cells

Pou6f2 is a genetic connection between central corneal thickness (CCT) in the mouse and a risk factor for developing primary open-angle glaucoma. POU6F2 is also a risk factor for several conditions in humans, including glaucoma, myopia, and dyslexia. Recent findings demonstrate that POU6F2-positive retinal ganglion cells (RGCs) comprise a number of RGC subtypes in the mouse, some of which also co-stain for Cdh6 and Hoxd10. These POU6F2-positive RGCs appear to be novel of ON–OFF directionally selective ganglion cells (ooDSGCs) that do not co-stain with CART or SATB2 (typical ooDSGCs markers). These POU6F2-positive cells are sensitive to damage caused by elevated intraocular pressure. In the DBA/2J mouse glaucoma model, heavily-labeled POU6F2 RGCs decrease by 73% at 8 months of age compared to only 22% loss of total RGCs (labeled with RBPMS). Additionally, Pou6f2−/− mice suffer a significant loss of acuity and spatial contrast sensitivity along with an 11.4% loss of total RGCs. In the rhesus macaque retina, POU6F2 labels the large parasol ganglion cells that form the magnocellular (M) pathway. The association of POU6F2 with the M-pathway may reveal in part its role in human glaucoma, myopia, and dyslexia.

Biomechanical Correlations Between the Cornea and the Optic Nerve Head.

A thin cornea is a potent risk factor for glaucoma. The underlying mechanisms remain unexplained. It has been postulated that central corneal thickness (CCT) may be a surrogate for biomechanical parameters of the posterior eye. In this study, we aimed to explore correlations of biomechanical responses between the cornea and the optic nerve head (ONH) and the peripapillary sclera (PPS) to elevated intraocular pressure (IOP), the primary risk factor of glaucoma. Inflation tests were performed in nine pairs of human donor globes. One eye of each pair was randomly assigned for cornea or posterior eye inflation. IOP was raised from 5 to 30 millimeters of mercury (mmHg) at 0.5 mmHg steps in the whole globe and the cornea or the ONH/PPS was imaged using a 50 MHz ultrasound probe. Correlation-based ultrasound speckle tracking was used to calculate tissue displacements and strains. Associations of radial, tangential, and shear strains at 30 mmHg between the cornea and the ONH or PPS were evaluated. Corneal shear strain was significantly correlated with ONH shear strain (R = 0.857, P = 0.003) and PPS shear strain (R = 0.724, P = 0.028). CCT was not correlated with any strains in the cornea, ONH, or PPS. Our results suggested that an eye that experiences a larger shear strain in the cornea would likely experience a larger shear strain in its ONH and PPS at IOP elevations. The strong correlation between the cornea's and the ONH's shear response to IOP provides new insights and suggests a plausible explanation of the cornea's connection to glaucoma risk.

Distribution of Intraocular Pressure in Indigenous Black Africans and Related Risk Factors: A Population-Based Study in Southwest Nigeria

Background: Elevated intraocular pressure (IOP) is a major risk factor for glaucoma and is presently the only modifiable risk factor. Even in a healthy population, IOP distribution varies among different racial groups. Objective: To determine the distribution of IOP and factors affecting it, among an indigenous African population in Southwest Nigeria. Methods: A population-based descriptive cross-sectional survey with an analytical component was performed. The study was conducted among participants 16 years and older who were residents of Akinyele Local Government Area of Oyo State and were all black Africans. A multi-stage sampling with probability proportional to size was used to identify the study population. All participants were examined at the local health center in their community, assessing the visual acuity, Goldmann applanation tonometry, central corneal thickness, anterior segment, fundoscopy, weight, height, and blood pressure. Results: A total of 1810 respondents completed the study; male patients accounted for 41.55%. Mean age was 49.43 ± 15.57 years. The mean IOP was 15.91 ± 4.74 mmHg. There was a significant association between elevated IOP and the male gender. Intraocular pressure also had a significant positive correlation with increasing age, systolic blood pressure, and central cornea thickness. There was no significant relationship between IOP and self-reported diabetes mellitus. Conclusion: The mean IOP and distribution in this study were a bit different from that observed in studies in different geographical locations but similar to studies in West Africa. It may be advisable to employ a geographical approach to normal IOP interpretation.

Genetic correlation between circulating cytokines and risk of three ophthalmic diseases: a bidirectional two-sample Mendelian randomization study.

Pathogenesis and the associated risk factors of cataracts, glaucoma, and age-related macular degeneration (AMD) remain unclear. We aimed to investigate causal relationships between circulating cytokine levels and the development of these diseases. Genetic instrumental variables for circulating cytokines were derived from a genome-wide association study of 8293 European participants. Summary-level data for AMD, glaucoma, and senile cataract were obtained from the FinnGen database. The inverse variance weighted (IVW) was the main Mendelian randomization (MR) analysis method. The Cochran's Q, MR-Egger regression, and MR pleiotropy residual sum and outlier test were used for sensitivity analysis. Based on the IVW method, MR analysis demonstrated five circulating cytokines suggestively associated with AMD (SCGF-β, 1.099 [95%CI, 1.037-1.166], P = 0.002; SCF, 1.155 [95%CI, 1.015-1.315], P = 0.029; MCP-1, 1.103 [95%CI, 1.012-1.202], P = 0.026; IL-10, 1.102 [95%CI, 1.012-1.200], P = 0.025; eotaxin, 1.086 [95%CI, 1.002-1.176], P = 0.044), five suggestively linked with glaucoma (MCP-1, 0.945 [95%CI, 0.894-0.999], P = 0.047; IL1ra, 0.886 [95%CI, 0.809-0.969], P = 0.008; IL-1β, 0.866 [95%CI, 0.762-0.983], P = 0.027; IL-9, 0.908 [95%CI, 0.841-0.980], P = 0.014; IL2ra, 1.065 [95%CI, 1.004-1.130], P = 0.035), and four suggestively associated with senile cataract (TRAIL, 1.043 [95%CI, 1.009-1.077], P = 0.011; IL-16, 1.032 [95%CI, 1.001-1.064], P = 0.046; IL1ra, 0.942 [95%CI, 0.887-0.999], P = 0.047; FGF-basic, 1.144 [95%CI, 1.052-1.244], P = 0.002). Furthermore, sensitivity analysis results supported the above associations. This study highlights the involvement of several circulating cytokines in the development ophthalmic diseases and holds potential as viable pharmacological targets for these diseases.

Smoking Intensity is Associated With Progressive Optic Nerve Head Vessel Density Loss in Glaucoma.

A lifetime history of greater smoking consumption was associated with faster vessel density loss over time. Smoking intensity should be considered when assessing the risk of glaucoma progression, as well as its management. To investigate the relationship of smoking and smoking intensity, with the rate of optic nerve head (ONH) whole image capillary density (wiCD) loss in primary open angle glaucoma (POAG) and glaucoma suspect patients. In this longitudinal study, patients with POAG who had at least 2 years of follow-up and optical coherence tomography angiography (OCTA) performed at a minimum of 4 visits were selected for study. The smoking intensity was calculated as the pack-year at the baseline OCTA. Univariable and multivariable linear mixed models were used to determine the effect of each parameter on the rates of wiCD loss over time. Nonlinear least-squares estimation with piecewise regression model was used to investigate the cutoff point for the relationship between wiCD loss and smoking intensity. One hundred sixty-four eyes (69 glaucoma suspect and 95 POAG) of 110 patients were included with a mean (95% CI) follow-up of 4.0 (3.9 to 4.1) years. Of the 110 patients, 50 (45.5%) had a reported history of smoking. Greater smoking intensity was associated with faster wiCD loss [-0.11 (-0.23 to 0.00)] %/year per 10 pack-year higher; P =0.048) after adjusting for covariates. The wiCD thinning became significantly faster when smoking intensity was greater than 22.2 pack-years. Smoking had no effect on the rate of wiCD thinning in patients who smoked <22.2 pack-years during their lifetime. A history of greater smoking consumption was associated with faster vessel density loss, suggesting smoking intensity as a potential risk factor for glaucoma.

Glaucoma Screening among Relatives of Glaucoma Patients in Anambra State, Nigeria

Aim: To determine the awareness, attitude, and practice of glaucoma screening among adult first degree relatives of glaucoma patients in Anambra State, Nigeria. Study Design: A prospective, descriptive, cross-sectional survey. Place of Study: Eye clinics and community eye care out-reaches that offer primary, secondary, and tertiary eye care services to people within Anambra state, Nigeria. Methods: A pretested, interviewer-administered questionnaire was used to obtain information such as sociodemographic data, awareness and knowledge of glaucoma and the frequency of practice of glaucoma screening. These were analyzed using descriptive and inferential statistics (Chi square test and logistic regression) where applicable. Level of significance was set at a p-value &lt;0.05. Results: A total of 186 first degree relatives (FDRs) of glaucoma patients participated, 120 (59.1%) were females, M: F = 1:1.4 and a mean age 43.87 years ± 14.62 SD. Almost half had a secondary level of education and were traders. Majority (83.9%) and 39.8% had heard of glaucoma and glaucoma screening respectively in the past. However, only 23.7% had been screened for glaucoma. The main reasons respondents gave why they did not screen for glaucoma include 'not necessary', 'no time' and ' not affordable. There was a significant negative relationship between unemployment and poor glaucoma screening practice p=0.007. Conclusion: This study showed a generally poor knowledge, attitude and practices towards glaucoma screening in the study population. Stakeholders need to intensify efforts to make people understand glaucoma risk factors and appreciate the need to have glaucoma screening in their environments.

A new mouse-fixation device for IOP measurement in awake mice

Glaucoma is an irreversible blinding eye disease. The mechanisms underlying glaucoma are complex. Up to now, no successful remedy has been found to completely cure the condition. High intraocular pressure (IOP) is an established risk factor for glaucoma and the only known modifiable factor for glaucoma treatment. Mice have been widely used to study glaucoma pathogenesis. IOP measurement is an important tool for monitoring the potential development of glaucomatous phenotypes in glaucoma mouse models. Currently, there are two methods of IOP measurement in mice: invasive and non-invasive. As the invasive method can cause corneal damage and inflammation, and most of the noninvasive method involves the use of anesthetics. In the course of our research, we designed a mouse fixation device to facilitate non-invasive measurements of mouse IOPs. Using this device, mouse IOPs can be accurately measured in awake mice. This device will help researchers to accurately assess mouse IOP without the use of anesthetics.

Aging and intraocular pressure homeostasis in mice.

Age and elevated intraocular pressure (IOP) are the two primary risk factors for glaucoma, an optic neuropathy that is the leading cause of irreversible blindness. In most people, IOP is tightly regulated over a lifetime by the conventional outflow tissues. However, the mechanistic contributions of age to conventional outflow dysregulation, elevated IOP and glaucoma are unknown. To address this gap in knowledge, we studied how age affects the morphology, biomechanical properties and function of conventional outflow tissues in C57BL/6 mice, which have an outflow system similar to humans. As reported in humans, we observed that IOP in mice was maintained within a tight range over their lifespan. Remarkably, despite a constellation of age-related changes to the conventional outflow tissues that would be expected to hinder aqueous drainage and impair homeostatic function (decreased cellularity, increased pigment accumulation, increased cellular senescence and increased stiffness), outflow facility, a measure of conventional outflow tissue fluid conductivity, was stable with age. We conclude that the murine conventional outflow system has significant functional reserve in healthy eyes. However, these age-related changes, when combined with other underlying factors, such as genetic susceptibility, are expected to increase risk for ocular hypertension and glaucoma.

Metformin in Glaucoma Treatment.

Rigorous trials are essential to develop comprehensive treatment strategies that fully exploit the therapeutic potential of metformin in the treatment of glaucoma. The objective of this study was to evaluate the potentially beneficial effect of metformin on glaucoma risk factors and to investigate the underlying mechanisms. The aim is to contribute to the development of new treatment strategies for glaucoma. We searched for studies that assessed the effects of metformin on glaucoma risk factors and the associated underlying mechanisms. Our search included electronic databases such as PUBMED, EMBASE, and clinicaltrials.gov. Unfortunately, we did not find any clinical trials that specifically investigated the impact of metformin on glaucoma. However, data from experimental studies demonstrated the capability of metformin to modulate various pathways that could contribute to neuroprotection in glaucoma. In order to develop comprehensive treatment strategies that fully exploit the therapeutic potential of metformin in the treatment of glaucoma, rigorous trials are essential. These studies are necessary to demonstrate both the safety and efficacy of metformin in the context of glaucoma treatment.