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Lancet (London, England) Nov 2023The glaucomas are a group of conditions leading to irreversible sight loss and characterised by progressive loss of retinal ganglion cells. Although not always elevated,... (Review)
Review
The glaucomas are a group of conditions leading to irreversible sight loss and characterised by progressive loss of retinal ganglion cells. Although not always elevated, intraocular pressure is the only modifiable risk factor demonstrated by large clinical trials. It remains the leading cause of irreversible blindness, but timely treatment to lower intraocular pressure is effective at slowing the rate of vision loss from glaucoma. Methods for lowering intraocular pressure include laser treatments, topical medications, and surgery. Although modern surgical innovations aim to be less invasive, many have been introduced with little supporting evidence from randomised controlled trials. Many cases remain undiagnosed until the advanced stages of disease due to the limitations of screening and poor access to opportunistic case finding. Future research aims to generate evidence for intraocular pressure-independent neuroprotective treatments, personalised treatment through genetic risk profiling, and exploration of potential advanced cellular and gene therapies.
Topics: Humans; Glaucoma, Open-Angle; Glaucoma; Intraocular Pressure; Blindness; Vision Disorders
PubMed: 37742700
DOI: 10.1016/S0140-6736(23)01289-8 -
Nature Communications Jan 2024Primary open-angle glaucoma (POAG), characterized by retinal ganglion cell death, is a leading cause of irreversible blindness worldwide. However, its molecular and...
Primary open-angle glaucoma (POAG), characterized by retinal ganglion cell death, is a leading cause of irreversible blindness worldwide. However, its molecular and cellular causes are not well understood. Elevated intraocular pressure (IOP) is a major risk factor, but many patients have normal IOP. Colocalization and Mendelian randomization analysis of >240 POAG and IOP genome-wide association study (GWAS) loci and overlapping expression and splicing quantitative trait loci (e/sQTLs) in 49 GTEx tissues and retina prioritizes causal genes for 60% of loci. These genes are enriched in pathways implicated in extracellular matrix organization, cell adhesion, and vascular development. Analysis of single-nucleus RNA-seq of glaucoma-relevant eye tissues reveals that the POAG and IOP colocalizing genes and genome-wide associations are enriched in specific cell types in the aqueous outflow pathways, retina, optic nerve head, peripapillary sclera, and choroid. This study nominates IOP-dependent and independent regulatory mechanisms, genes, and cell types that may contribute to POAG pathogenesis.
Topics: Humans; Genome-Wide Association Study; Glaucoma, Open-Angle; Gene Expression Regulation; Causality; Glaucoma
PubMed: 38195602
DOI: 10.1038/s41467-023-44380-y -
Molecular Aspects of Medicine Dec 2023Glaucoma is a common irreversible vision loss disorder because of the gradual loss of retinal ganglion cells (RGCs) and the optic nerve axons. Major risk factors include... (Review)
Review
Glaucoma is a common irreversible vision loss disorder because of the gradual loss of retinal ganglion cells (RGCs) and the optic nerve axons. Major risk factors include elder age and high intraocular pressure (IOP). However, high IOP is neither necessary nor sufficient to cause glaucoma. Some non-IOP signaling cascades can mediate RGC degeneration. In addition, gender, diet, obesity, depression, or anxiety also contribute to the development of glaucoma. Understanding the mechanism of glaucoma development is crucial for timely diagnosis and establishing new strategies to improve current IOP-reducing therapies. The microbiota exerts a marked influence on the human body during homeostasis and disease. Many glaucoma patients have abnormal compositions of the microbiota (dysbiosis) in multiple locations, including the ocular surface, intraocular cavity, oral cavity, stomach, and gut. Here, we discuss findings in the last ten years or more about the microbiota and metabolite changes in animal models, patients with three risk factors (aging, obesity, and depression), and glaucoma patients. Antigenic mimicry and heat stress protein (HSP)-specific T-cell infiltration in the retina may be responsible for commensal microbes contributing to glaucomatous RGC damage. LPS-TLR4 pathway may be the primary mechanism of oral and ocular surface dysbiosis affecting glaucoma. Microbe-derived metabolites may also affect glaucoma pathogenesis. Homocysteine accumulation, inflammatory factor release, and direct dissemination may link gastric H. pylori infection and anterior chamber viral infection (such as cytomegalovirus) to glaucoma. Potential therapeutic protocols targeting microbiota include antibiotics, modified diet, and stool transplant. Later investigations will uncover the underlying molecular mechanism connecting dysbiosis to glaucoma and its clinical applications in glaucoma management.
Topics: Animals; Humans; Aged; Dysbiosis; Glaucoma; Retina; Microbiota; Obesity; Disease Models, Animal
PubMed: 37866106
DOI: 10.1016/j.mam.2023.101221 -
International Journal of Molecular... Jun 2023Elevated levels of homocysteine (Hcy), a non-proteinogenic amino acid, may lead to a host of manifestations across the biological systems, particularly the nervous... (Review)
Review
Elevated levels of homocysteine (Hcy), a non-proteinogenic amino acid, may lead to a host of manifestations across the biological systems, particularly the nervous system. Defects in Hcy metabolism have been associated with many neurodegenerative diseases including glaucoma, i.e., the leading cause of blindness. However, the pathophysiology of elevated Hcy and its eligibility as a risk factor for glaucoma remain unclear. We aimed to provide a comprehensive review of the relationship between elevated Hcy levels and glaucoma. Through a systemic search of the PubMed and Google Scholar databases, we found that elevated Hcy might play an important role in the pathogenesis of glaucoma. Further research will be necessary to help clarify the specific contribution of elevated Hcy in the pathogenesis of glaucoma. A discovery and conceptual understanding of Hcy-associated glaucoma could be the keys to providing better therapeutic treatment, if not prophylactic treatment, for this disease.
Topics: Humans; Glaucoma, Open-Angle; Glaucoma; Amino Acids; Risk Factors; Homocysteine
PubMed: 37445966
DOI: 10.3390/ijms241310790 -
Klinische Monatsblatter Fur... Aug 2023Angle-closure glaucoma is a less common form of glaucoma in Europe than open-angle glaucoma. Nevertheless, the clinical picture should also be known here since it can...
Angle-closure glaucoma is a less common form of glaucoma in Europe than open-angle glaucoma. Nevertheless, the clinical picture should also be known here since it can lead to severe visual disturbances and even blindness within a short time. It is divided into primary and secondary forms and can be further categorized depending on the presence of a pupillary block. In all cases, therapy is initially based on resolving the cause of the angle-closure and treating any underlying disease that may be present. In addition, intraocular pressure reduction must be achieved. This can be effectuated conservatively or surgically. Depending on the specific subtype of angle-closure, different treatments are promising.
Topics: Humans; Glaucoma, Angle-Closure; Glaucoma, Open-Angle; Blindness; Pupil Disorders; Europe; Intraocular Pressure
PubMed: 37236235
DOI: 10.1055/a-1812-4381 -
Biomedicine & Pharmacotherapy =... Dec 2023Glaucoma is the world's leading irreversible blinding eye disease. Lowering intraocular pressure is currently the only effective clinical treatment. However, there is a... (Review)
Review
Glaucoma is the world's leading irreversible blinding eye disease. Lowering intraocular pressure is currently the only effective clinical treatment. However, there is a lack of long-acting IOP-lowering drugs, and some patients still experience retinal ganglion cell loss even with good intraocular pressure control. Currently, there is no effective method for neuroprotection and regeneration in clinical practice for glaucoma. In recent years, epigenetics has been widely researched and reported for its role in glaucoma's neuroprotection and regeneration. This article reviews the changes in histone modifications, DNA methylation, non-coding RNA, and m6A methylation in glaucoma, aiming to provide new perspectives for glaucoma management, protection of retinal ganglion cells, and axon regeneration by understanding epigenetic alterations.
Topics: Humans; Axons; Epigenesis, Genetic; Nerve Regeneration; Glaucoma; Intraocular Pressure
PubMed: 37806089
DOI: 10.1016/j.biopha.2023.115633 -
Acta Ophthalmologica Mar 2024Glaucoma is currently considered one of the leading causes of severe visual impairment and blindness worldwide. Topical medical therapy represents the treatment of... (Review)
Review
Glaucoma is currently considered one of the leading causes of severe visual impairment and blindness worldwide. Topical medical therapy represents the treatment of choice for many glaucoma patients. Introduction of latanoprost, 25 years ago, with an entirely new mechanism of action from that of the antiglaucoma drugs used up to that time was a very important milestone. Since then, due mainly to their efficacy, limited systemic side effects and once daily dosing, prostaglandin analogues (PGAs) have become as the first-choice treatment for primary open-angle glaucoma. PGAs are in general terms well tolerated, although they are associated with several mild to moderate ocular and periocular adverse events. Among them, conjunctival hyperemia, eyelash changes, eyelid pigmentation, iris pigmentation and hypertrichosis around the eyes are the most prevalent. The objective of this paper is to review the role of PGAs in the treatment of glaucoma over the 25 years since the launch of Latanoprost and their impact on clinical practice outcomes.
Topics: Humans; Latanoprost; Glaucoma, Open-Angle; Prostaglandins F, Synthetic; Antihypertensive Agents; Glaucoma; Prostaglandins, Synthetic; Ocular Hypertension; Intraocular Pressure
PubMed: 37350260
DOI: 10.1111/aos.15725 -
Progress in Retinal and Eye Research Sep 2023Glaucoma is defined by characteristic optic nerve damage and corresponding visual field defects and is the leading cause of irreversible blindness in the world. Elevated... (Review)
Review
Glaucoma is defined by characteristic optic nerve damage and corresponding visual field defects and is the leading cause of irreversible blindness in the world. Elevated intraocular pressure (IOP) is a strong risk factor for developing glaucoma. However, glaucoma can occur at any IOP. Normal tension glaucoma (NTG) arises with IOPs that are within what has been defined as a normal range, i.e., 21 mm Hg or less, which may present challenges in its diagnosis and management. Identifying inheritance patterns and genetic mutations in families with NTG has helped elucidate mechanisms of NTG, however the pathophysiology is complex and not fully understood. Approximately 2% of NTG cases are caused primarily by mutations in single genes, optineurin (OPTN), TANK binding kinase 1 (TKB1), or myocilin (MYOC). Herein, we review pedigree studies of NTG and autosomal dominant NTG caused by OPTN, TBK1, and MYOC mutations. We review identified mutations and resulting clinical features of OPTN-associated and TBK1-associated NTG, including long-term follow up of these patients with NTG. In addition, we report a new four-generation pedigree of NTG caused by a Glu50Lys OPTN mutation, including six family members with a mean follow up of 17 years. Common features of OPTN -associated NTG due to Glu50Lys mutation included early onset of disease with an IOP <21 mm Hg, marked optic disc cupping, and progressive visual field loss which appeared to stabilize once an IOP of less than 10 mm Hg was achieved. Lastly, we review risk factor genes which have been identified to contribute to the complex inheritance of NTG.
Topics: Humans; Low Tension Glaucoma; Glaucoma; Optic Disk; Mutation; Blindness; Vision Disorders; Intraocular Pressure
PubMed: 37353142
DOI: 10.1016/j.preteyeres.2023.101191 -
Frontiers in Immunology 2023Autoimmunity and inflammation are the main characteristics of rheumatic diseases and have both been found to be related to glaucoma. However, it remains unclear whether...
BACKGROUND
Autoimmunity and inflammation are the main characteristics of rheumatic diseases and have both been found to be related to glaucoma. However, it remains unclear whether rheumatic diseases increase the risk of glaucoma. Here, we performed a Mendelian randomization (MR) analysis to investigate the causal effects of six common rheumatic diseases on glaucoma.
METHODS
Six rheumatic diseases were included: ankylosing spondylitis (AS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sicca syndrome/Sjögren's sydrome (SS), dermatomyositis (DM), and gout. Glaucoma included primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG). Genetic variants associated with these rheumatic diseases and glaucoma were extracted from the genome-wide association studies and FinnGen8 database, respectively. First, a two-sample MR was used to investigate the potential causal association. Then, a multivariable MR was conducted to further verify the results. Inverse-variance weighted MR analysis was used as the main method, together with several sensitivity analyses.
RESULTS
Two-sample MR suggests that AS is related to a higher risk of both POAG [odds ratio (OR): 1.28, 95% confidence interval (CI) 1.13-1.44; = 1.1 × 10] and PACG (OR: 1.55, 95% CI: 1.09-2.09, = 1.4 × 10). Multivariable MR shows a similar trend of the effect of AS on POAG (OR: 1.52, 95% CI: 1.22-1.90, = 1.9 × 10) and PACG (OR: 2.05, 95% CI: 1.06-3.95, = 3.2 × 10). No significant association was observed between the other five rheumatic diseases and glaucoma.
CONCLUSIONS
AS is related to an increased risk of POAG and PACG. We stress the importance of glaucoma screening for AS patients.
Topics: Humans; Glaucoma, Open-Angle; Genome-Wide Association Study; Mendelian Randomization Analysis; Glaucoma; Arthritis, Rheumatoid
PubMed: 37799717
DOI: 10.3389/fimmu.2023.1227138 -
Ugeskrift For Laeger Nov 2023This review offers a summary of the current knowledge of pshychotropic drugs and glaucoma. If exposed to psychotropic drugs, some patients may develop angle-closure... (Review)
Review
This review offers a summary of the current knowledge of pshychotropic drugs and glaucoma. If exposed to psychotropic drugs, some patients may develop angle-closure glaucoma. Although rarely contraindicated, exposed predisposed and diagnosed patients should be followed-up by an ophthalmologist. It is still unclear if serotonin reuptake inhibitors increase the risk of angle-closure glaucoma. Tricyclic antidepressants and benzodiazepines should be used with caution in predisposed patients. The same applies to antipsychotic drugs, where first-generation antipsychotic drugs might have a smaller impact on the intraocular pressure than second-generation antipsychotic drugs.
Topics: Humans; Antipsychotic Agents; Glaucoma, Angle-Closure; Psychotropic Drugs; Glaucoma; Selective Serotonin Reuptake Inhibitors
PubMed: 38018726
DOI: No ID Found