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Nature Communications May 2023Glaucoma is a progressive optic neuropathy and a leading cause of irreversible blindness worldwide. Primary open-angle glaucoma is the most common form, and yet the...
Glaucoma is a progressive optic neuropathy and a leading cause of irreversible blindness worldwide. Primary open-angle glaucoma is the most common form, and yet the etiology of this multifactorial disease is poorly understood. We aimed to identify plasma metabolites associated with the risk of developing POAG in a case-control study (599 cases and 599 matched controls) nested within the Nurses' Health Studies, and Health Professionals' Follow-Up Study. Plasma metabolites were measured with LC-MS/MS at the Broad Institute (Cambridge, MA, USA); 369 metabolites from 18 metabolite classes passed quality control analyses. For comparison, in a cross-sectional study in the UK Biobank, 168 metabolites were measured in plasma samples from 2,238 prevalent glaucoma cases and 44,723 controls using NMR spectroscopy (Nightingale, Finland; version 2020). Here we show higher levels of diglycerides and triglycerides are adversely associated with glaucoma in all four cohorts, suggesting that they play an important role in glaucoma pathogenesis.
Topics: Humans; Glaucoma, Open-Angle; Case-Control Studies; Cross-Sectional Studies; Follow-Up Studies; Biological Specimen Banks; Chromatography, Liquid; Tandem Mass Spectrometry; United Kingdom
PubMed: 37208353
DOI: 10.1038/s41467-023-38466-w -
Eye (London, England) Jan 2020Presentation with advanced glaucoma is a significant risk factor for lifetime blindness. The asymptomatic nature of glaucoma, particularly in early disease, means that... (Review)
Review
Presentation with advanced glaucoma is a significant risk factor for lifetime blindness. The asymptomatic nature of glaucoma, particularly in early disease, means that substantial vision loss in one eye does not always translate into a perceptible loss of visual function. This, along with the lack of an effective screening strategy, contributes to late presentation. Those most at risk of presenting with advanced glaucoma have asymptomatic high intraocular pressure (IOP), no family history of glaucoma, are socially disadvantaged, and do not attend sight testing. Patients with glaucoma may have impaired functionality for daily activities, such as reading, walking and driving. Quality of life measures have shown this to be significantly worse in patients with more severe visual field loss, particularly if bilateral. In addition, quality of life decreases faster with further bilateral visual field loss when advanced visual field damage is present. Management of these patients requires disproportionally more resources than those with earlier disease. Both medical and surgical options are used as the initial approach to treat patients presenting with advanced glaucoma. The most recently published National Institute for Health and Care Excellence (NICE) guidelines suggest that patients presenting with advanced disease should be offered trabeculectomy as a primary intervention. However, more evidence is required to determine the best initial management. The Treatment of Advanced Glaucoma Study (TAGS) is being conducted, comparing primary medical management with primary mitomycin C-augmented trabeculectomy for people presenting with advanced open-angle glaucoma. The results of TAGS will provide robust evidence for the most appropriate initial intervention.
Topics: Antihypertensive Agents; Glaucoma; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Quality of Life; Trabeculectomy
PubMed: 31740802
DOI: 10.1038/s41433-019-0637-2 -
Scientific Reports Nov 2023Several observational studies have investigated the association between cannabis use and intraocular pressure, but its association with primary open-angle glaucoma... (Meta-Analysis)
Meta-Analysis
Several observational studies have investigated the association between cannabis use and intraocular pressure, but its association with primary open-angle glaucoma (POAG) remains unclear. In this study, we leveraged human genetic data to assess through Mendelian randomization (MR) whether cannabis use affects POAG. We used five single-nucleotide polymorphisms (SNPs) associated with lifetime cannabis use (P-value < 5 × 10) from a genome-wide association study (GWAS) (N = 184,765) by the International Cannabis Consortium, 23andMe, and UK Biobank and eleven SNPs associated with cannabis use disorder (P-value < 5 × 10) from a GWAS meta-analysis of (17,068 cases and 357,219 controls of European descent) from Psychiatric Genomics Consortium Substance Use Disorders working group, Lundbeck Foundation Initiative for Integrative Psychiatric Research, and deCode. We associated the selected five SNPs from the GWAS of lifetime cannabis use and the eleven SNPs from the GWAS of cannabis use disorder, with the largest to date GWAS meta-analysis of POAG (16,677 cases and 199,580 controls). MR analysis suggested no evidence for a causal association of lifetime cannabis use and cannabis use disorder with POAG (odds ratio (OR) of outcome per doubling of the odds of exposure (95% confidence interval): 1.04 (0.88; 1.23) for lifetime cannabis use and 0.97 (0.92; 1.03) for cannabis use disorder). Sensitivity analyses to address pleiotropy and weak instrument bias yielded similar estimates to the primary analysis. In conclusion, our results do not support a causal association between cannabis use and POAG.
Topics: Humans; Genome-Wide Association Study; Cannabis; Mendelian Randomization Analysis; Glaucoma, Open-Angle; Marijuana Abuse; Polymorphism, Single Nucleotide
PubMed: 37949880
DOI: 10.1038/s41598-023-45872-z -
Journal of Glaucoma Feb 2022The Faroe Islands are home to 50,000 genetically isolated people in the North Atlantic. The prevalence of open-angle glaucoma (OAG) in the Faroese population is unknown....
PURPOSE
The Faroe Islands are home to 50,000 genetically isolated people in the North Atlantic. The prevalence of open-angle glaucoma (OAG) in the Faroese population is unknown. Consequently, we conducted a survey to determine the prevalence of OAG in the Faroese population. We also investigated the role of known glaucoma-causing genes in Faroese OAG.
MATERIALS AND METHODS
We conducted a prospective survey of known and newly diagnosed glaucoma patients at the Faroese National Hospital, Landssjukrahusid, Tórshavn between October 1, 2015 to December 31, 2017. In addition we reviewed the only eye care provider in the Faroese Islands by scrutinizing electronic medical records between 2009 and June 15, 2014, October 1, 2015 and the partly overlapping prescriptions for ocular hypotensive medications in 2016 to identify patients with either a diagnosis of glaucoma, a diagnosis of ocular hypertension or a prescription for ocular hypotensive medications. Next, we prospectively confirmed diagnoses with complete eye examinations. Patient DNA samples were tested for variations in known glaucoma-causing genes [myocilin (MYOC), optineurin (OPTN), and TANK binding kinase 1 (TBK1)].
RESULTS
We determined the age-related prevalence of OAG January 1, 2017 in individuals 40 years or older to be 10.7/1000 (1.07%) and highly age-related. A diagnosis of OAG was present in 264 patients, of whom 211 (79.9%) had primary OAG (including normal tension glaucoma), 49 (18.6%) had pseudoexfoliation glaucoma, and 4 (1.5%) had pigmentary glaucoma. Among patients receiving medications for glaucoma, nearly 50% had primary OAG, while the majority of the rest had ocular hypertension or secondary glaucoma. No disease-causing variants were detected in MYOC, OPTN, or TBK1.
CONCLUSIONS
The calculated prevalence of OAG in the Faroe Islands was 1.07%. The absence of MYOC, OPTN, or TBK1 disease-causing variants in Faroese primary OAG patients suggests that a different, potentially unique set of genes may be contributing to the pathogenesis of glaucoma in this population.
Topics: Adult; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Ocular Hypertension; Prevalence; Prospective Studies
PubMed: 34342283
DOI: 10.1097/IJG.0000000000001921 -
American Journal of Ophthalmology Aug 2021To evaluate the effect of population screening on low vision and blindness from open-angle glaucoma.
PURPOSE
To evaluate the effect of population screening on low vision and blindness from open-angle glaucoma.
DESIGN
Retrospective cohort study.
METHODS
A large population-based screening for glaucoma was conducted in Malmö, Sweden, from 1992 to 1997. A total of 42,497 subjects were invited, of which 32,918 were screened, and 9,579 were non-responders (ie, did not participate). The records of glaucoma patients who had visited the Department of Ophthalmology at Malmö University Hospital from January 1, 1987, to December 31, 2017, were reviewed. Patients diagnosed at or after the screening were assessed for moderate or severe vision impairment, here called low vision, or blindness by the World Health Organization definition. Selection bias was corrected by creating a group of potential screening participants from a comparison group of clinical patients. Main outcome measures were the risk ratios of the cumulative incidence for bilateral low vision or blindness caused by glaucoma in screened patients compared with the potential participants.
RESULTS
The cumulative incidence of blindness was 0.17% in the screened population versus 0.32% among the potential participants; and for low vision 0.25% versus 0.53%. The risk ratio (95% confidence interval) between the two was 0.52 (0.32-0.84) for blindness and 0.46 (0.31-0.68) for low vision. There were no differences between the proportions of potential confounders in the comparison group and those in the non-responders.
CONCLUSIONS
The results suggest that population screening may reduce bilateral low vision and blindness caused by glaucoma by approximately 50%.
Topics: Aged; Aged, 80 and over; Blindness; Female; Follow-Up Studies; Glaucoma, Open-Angle; Humans; Incidence; Intraocular Pressure; Male; Mass Screening; Retrospective Studies; Sweden; Visual Acuity; Visually Impaired Persons
PubMed: 33823158
DOI: 10.1016/j.ajo.2021.03.030 -
Cells Oct 2023The glucocorticoid receptor (GR), including both alternative spliced isoforms (GRα and GRβ), has been implicated in the development of primary open-angle glaucoma... (Review)
Review
The glucocorticoid receptor (GR), including both alternative spliced isoforms (GRα and GRβ), has been implicated in the development of primary open-angle glaucoma (POAG) and iatrogenic glucocorticoid-induced glaucoma (GIG). POAG is the most common form of glaucoma, which is the leading cause of irreversible vision loss and blindness in the world. Glucocorticoids (GCs) are commonly used therapeutically for ocular and numerous other diseases/conditions. One serious side effect of prolonged GC therapy is the development of iatrogenic secondary ocular hypertension (OHT) and OAG (i.e., GC-induced glaucoma (GIG)) that clinically and pathologically mimics POAG. GC-induced OHT is caused by pathogenic damage to the trabecular meshwork (TM), a tissue involved in regulating aqueous humor outflow and intraocular pressure. TM cells derived from POAG eyes (GTM cells) have a lower expression of GRβ, a dominant negative regulator of GC activity, compared to TM cells from age-matched control eyes. Therefore, GTM cells have a greater pathogenic response to GCs. Almost all POAG patients develop GC-OHT when treated with GCs, in contrast to a GC responder rate of 40% in the normal population. An increased expression of GRβ can block GC-induced pathogenic changes in TM cells and reverse GC-OHT in mice. The endogenous expression of GRβ in the TM may relate to differences in the development of GC-OHT in the normal population. A number of studies have suggested increased levels of endogenous cortisol in POAG patients as well as differences in cortisol metabolism, suggesting that GCs may be involved in the development of POAG. Additional studies are warranted to better understand the molecular mechanisms involved in POAG and GIG in order to develop new disease-modifying therapies to better treat these two sight threatening forms of glaucoma. The purpose of this timely review is to highlight the pathological and clinical features of GC-OHT and GIG, mechanisms responsible for GC responsiveness, potential therapeutic options, as well as to compare the similar features of GIG with POAG.
Topics: Humans; Mice; Animals; Glucocorticoids; Receptors, Glucocorticoid; Glaucoma, Open-Angle; Hydrocortisone; Glaucoma; Ocular Hypertension; Iatrogenic Disease
PubMed: 37887296
DOI: 10.3390/cells12202452 -
Acta Ophthalmologica Mar 2022The aim of this article is to discuss how physiology and anatomical background affect the effectiveness of implant-dependent microinvasive glaucoma surgery (MIGS).... (Review)
Review
The aim of this article is to discuss how physiology and anatomical background affect the effectiveness of implant-dependent microinvasive glaucoma surgery (MIGS). First, we provide a micro view of aqueous outflow and tissue behaviour. Second, we review studies exploring the mechanisms of the pressure-lowering effect of MIGS, as well as tissue behaviour during aqueous flow and tissue motion. We also describe and classify microinvasive surgical procedures and the most important types of implants, as well as their mechanisms of action, implantation techniques and efficacy. Further, we summarize the indications and surgical results presented in recent studies, providing an evidence-based update on novel and emerging MIGS techniques for the treatment of open-angle glaucoma. These data can help surgeons to personalize the management of glaucoma and to choose the best MIGS option for individual glaucoma patients.
Topics: Glaucoma Drainage Implants; Glaucoma, Open-Angle; Humans; Latanoprost; Minimally Invasive Surgical Procedures; Ophthalmic Solutions
PubMed: 33988310
DOI: 10.1111/aos.14906 -
European Journal of Pharmacology Sep 2023Glaucoma is a chronic and progressive neurodegenerative disease characterized by the loss of retinal ganglion cells and visual field defects, and currently affects... (Review)
Review
Glaucoma is a chronic and progressive neurodegenerative disease characterized by the loss of retinal ganglion cells and visual field defects, and currently affects around 1% of the world's population. Elevated intraocular pressure (IOP) is the best-known modifiable risk factor and a key therapeutic target in hypertensive glaucoma. The trabecular meshwork (TM) is the main site of aqueous humor outflow resistance and therefore a critical regulator of IOP. Fibrosis, a reparative process characterized by the excessive deposition of extracellular matrix components and contractile myofibroblasts, can impair TM function and contribute to the pathogenesis of primary open-angle glaucoma (POAG) as well as the failure of minimally invasive glaucoma surgery (MIGS) devices. This paper provides a detailed overview of the current anti-fibrotic therapeutics targeting the TM in glaucoma, along with their anti-fibrotic mechanisms, efficacy as well as the current research progress from pre-clinical to clinical studies.
Topics: Humans; Trabecular Meshwork; Glaucoma, Open-Angle; Neurodegenerative Diseases; Intraocular Pressure; Glaucoma; Aqueous Humor
PubMed: 37391006
DOI: 10.1016/j.ejphar.2023.175882 -
Molecular Medicine Reports Aug 2020Glaucoma is a group of progressive optic neuropathies that have in common characteristic optic nerve head changes, loss of retinal ganglion cells and visual field... (Review)
Review
Glaucoma is a group of progressive optic neuropathies that have in common characteristic optic nerve head changes, loss of retinal ganglion cells and visual field defects. Among the large family of glaucomas, primary open‑angle glaucoma (POAG) is the most common type, a complex and heterogeneous disorder with environmental and genetic factors contributing to its pathogenesis. Approximately 5% of POAG is currently attributed to single‑gene or Mendelian forms of glaucoma. Genetic linkage analysis and genome‑wide association studies have identified various genomic loci, paving the path to understanding the pathogenesis of this enigmatic, blinding disease. In this review we summarize the most common variants reported thus far and their possible clinical correlations.
Topics: Databases, Bibliographic; Endophenotypes; Genetic Linkage; Genetic Predisposition to Disease; Genome-Wide Association Study; Glaucoma, Open-Angle; Humans; Polymorphism, Single Nucleotide
PubMed: 32626970
DOI: 10.3892/mmr.2020.11215 -
Clinical & Experimental Optometry May 2022Systemic hypertension or hypertension is a very common chronic age-related disease worldwide. It is typically characterised by a sustained elevation of blood pressure,...
Systemic hypertension or hypertension is a very common chronic age-related disease worldwide. It is typically characterised by a sustained elevation of blood pressure, particularly when the systolic blood pressure and/or diastolic blood pressure are of more than 140 mmHg and 90 mmHg, respectively. If hypertension is not well controlled, it may lead to an increased risk of stroke and heart attack. It has been shown that hypertension is linked to various ocular diseases, including cataract, diabetic retinopathy, age-related macular degeneration, and glaucoma. Glaucoma is the leading cause of irreversible blindness worldwide. Primary open angle glaucoma is the most common form of the disease and is usually characterised by an increase in intraocular pressure. This condition, together with normal tension glaucoma, constitutes open angle glaucoma. Systemic hypertension has been identified as a risk factor for open angle glaucoma. It is speculated that blood pressure is involved in the pathogenesis of open angle glaucoma by altering intraocular pressure or ocular blood flow, or both. Recent evidence has shown that both extremely high and low blood pressure are associated with increased risk of open angle glaucoma. Additional pathogenic mechanisms, including increased inflammation likely to be involved in the development and progression of these two diseases, are discussed.
Topics: Blood Pressure; Glaucoma, Open-Angle; Humans; Hypertension; Intraocular Pressure; Ocular Hypertension; Tonometry, Ocular
PubMed: 34402761
DOI: 10.1080/08164622.2021.1964332