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Ophthalmic Research 2017To analyse drug development for open-angle glaucoma during the last 20 years. (Review)
Review
OBJECTIVES
To analyse drug development for open-angle glaucoma during the last 20 years.
METHODS
Research was performed by referring to clinical trials registered at the International Clinical Trials Registry Platform (ICTRP). A search for the condition "open-angle glaucoma" with the intervention "drug" was performed. We included trials registered from 01/01/1995 to 01/01/2015, only involving studies in phases 1, 2, and 3. Only studies resorting to novel treatment strategies (either novel drugs or yet-untested fixed associations of approved medication) were considered.
RESULTS
We recorded 158 studies for the condition of open-angle glaucoma with a drug-based intervention; 65 of the studies reported phase 2 trials and 74 reported phase 3 trials. Pharmaceutical companies were the primary sponsors of 95.3% of the trials. Most of the studies (66.5%, n = 105) involved a new drug, and the remainder (33.5%, n = 53) tested fixed drug associations. The bulk of the trials (n = 99, 62.7%) involved the use of prostaglandin analogues, either as a comparator or a study drug. In descending order of frequency, the studies conducted involved Rho-kinase inhibitors (n = 15), carbonic anhydrase inhibitors (n = 14), β-blockers (n = 7), angiostatic steroids (n = 6), α2-adrenergic agonists (n = 4), 5-HT2A receptor agonists (n = 4), and NMDA receptor antagonists (n = 2). A cyclin-dependent kinase inhibitor, an LIM-domain kinase 2 inhibitor, an A1 adenosine receptor agonist, catechin, macrolide, saffron, and seawater were each tested in 1 clinical trial.
CONCLUSION
Research into the medical treatment of glaucoma indicates the use of prostaglandin analogues. However, there are a significant number of trials testing other drug classes, particularly Rho-kinase inhibitors. This new focus could lead to a potential increase in the number of therapeutical options for the management of glaucoma in the future.
Topics: Adrenergic beta-Antagonists; Carbonic Anhydrase Inhibitors; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Randomized Controlled Trials as Topic; Registries
PubMed: 28076854
DOI: 10.1159/000453527 -
Cells Nov 2019Primary open angle glaucoma (POAG) is the most common form of glaucoma and the 2nd most common cause of irreversible vision loss in the United States. Nearly 67 million... (Review)
Review
Primary open angle glaucoma (POAG) is the most common form of glaucoma and the 2nd most common cause of irreversible vision loss in the United States. Nearly 67 million people have the disease worldwide including >3 million in the United States. A major risk factor for POAG is an elevation in intraocular pressure (IOP). The increase in IOP is believed to be caused by an increase in the deposition of extracellular matrix proteins, in particular fibronectin, in a region of the eye known as the trabecular meshwork (TM). How fibronectin contributes to the increase in IOP is not well understood. The increased density of fibronectin fibrils is thought to increase IOP by altering the compliance of the trabecular meshwork. Recent studies, however, also suggest that the composition and organization of fibronectin fibrils would affect IOP by changing the cell-matrix signaling events that control the functional properties of the cells in the trabecular meshwork. In this article, we will discuss how changes in the properties of fibronectin and fibronectin fibrils could contribute to the regulation of IOP.
Topics: Animals; Biomarkers; Disease Susceptibility; Extracellular Matrix; Fibronectins; Gene Expression; Glaucoma, Open-Angle; Humans; Protein Aggregates; Protein Aggregation, Pathological; Trabecular Meshwork
PubMed: 31779192
DOI: 10.3390/cells8121518 -
International Journal of Environmental... Jan 2022While exposure to pesticides is a known risk factor for neurodegenerative brain diseases, little is known about the influence of environment on glaucoma neuropathy. We...
While exposure to pesticides is a known risk factor for neurodegenerative brain diseases, little is known about the influence of environment on glaucoma neuropathy. We aimed to determine whether farmers are at higher risk of developing severe primary open-angle glaucoma (POAG). This retrospective cohort study (tertiary referral center, Reims University Hospital, France) included patients diagnosed with POAG in the last two years. Univariate analysis and adjusted multivariate logistic regression were performed to evaluate the association between agricultural profession and all recorded data. Glaucoma severity (primary outcome) and the number of patients who underwent filtering surgery (secondary outcome) were analyzed. In total, 2065 records were screened, and 772 patients were included (66 in the farmer group and 706 in the nonfarmer group). The risk of severe glaucoma was higher in the farmer group (adjusted odds ratio (aOR) 1.87, = 0.03). More patients underwent filtering surgery in the farmer group in univariate analysis ( = 0.02) but with no statistical significance after adjustment ( = 0.08). These results suggest pesticide exposure may be a factor accelerating the neurodegeneration in POAG, although a direct link between the agricultural profession and the disease requires further extended studies to be demonstrated.
Topics: Glaucoma, Open-Angle; Humans; Logistic Models; Pesticides; Retrospective Studies; Risk Factors
PubMed: 35055748
DOI: 10.3390/ijerph19020926 -
Experimental Eye Research Nov 2019Affecting nearly 80 million individuals, glaucoma is the number one cause of irreversible blindness in the world. This ocular disease describes a set of optic... (Review)
Review
Affecting nearly 80 million individuals, glaucoma is the number one cause of irreversible blindness in the world. This ocular disease describes a set of optic neuropathies of which primary open angle glaucoma (POAG) is the most common. POAG is associated with progressive visual field deterioration resulting from damage to the optic nerve and loss of retinal ganglion cells. Risk factors for POAG include elevated intraocular pressure, aging, African and Hispanic ancestry, and a positive family history of POAG. Multiple genes have been found to contribute to POAG. Much of POAG genetics and pathology has yet to be explained. Recent genome-wide association studies have identified a large number of novel loci associated with POAG and its endophenotypes. Genomic and proteomic profiling of biofluids has contributed to our knowledge of differential gene expression in POAG. Functional studies both in cell culture and animal models have confirmed the effects of variants and differential gene expression on ocular physiology while in silico analyses have increased our understanding of disease risk and progression so that we might better diagnose and treat this complex genetic illness.
Topics: Animals; Genetic Predisposition to Disease; Genome-Wide Association Study; Genomics; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Proteomics; Vision Disorders; Visual Fields
PubMed: 31525344
DOI: 10.1016/j.exer.2019.107795 -
Seminars in Ophthalmology 2016This article's objective is to provide an overview of the association between estrogen and glaucoma. A literature synthesis was conducted of articles published in... (Review)
Review
This article's objective is to provide an overview of the association between estrogen and glaucoma. A literature synthesis was conducted of articles published in peer-reviewed journals screened through May 5, 2015, using the PubMed database. Keywords used were "estrogen and glaucoma," "reproductive factors and glaucoma," and "estrogen, nitric oxide and eye." Forty-three journal articles were included. Results indicated that markers for lifetime estrogen exposure have been measured by several studies and show that the age of menarche onset, oral contraceptive (OC) use, bilateral oophorectomy, age of menopause onset and duration between menarche to menopause are associated with primary open-angle glaucoma (POAG) risk. The Blue Mountain Eye Study found a significantly increased POAG risk with later (>13 years) compared with earlier (≤12 years) age of menarche. Nurses' Health Study (NHS) investigators found that OC use of greater than 5 years was associated with a 25% increased risk of POAG. The Mayo Clinic Cohort Study of Oophorectomy and Aging found that women who underwent bilateral oophorectomy before age 43 years had an increased risk of glaucoma. The Rotterdam Study found that women who went through menopause before reaching the age of 45 years had a higher risk of open-angle glaucoma (2.6-fold increased risk), while the NHS showed a reduced risk of POAG among women older than 65 who entered menopause after age ≥ 54 years. Increased estrogen states may confer a reduced risk of glaucoma or glaucoma-related traits such as reduced intraocular pressure (IOP). Pregnancy, a hyperestrogenemic state, is associated with decreased IOP during the third trimester. Though the role of postmenopausal hormone (PMH) use in the reduction of IOP is not fully conclusive, PMH use may reduce the risk of POAG. From a genetic epidemiologic perspective, estrogen metabolic pathway single nucleotide polymorphisms (SNPs) were associated with POAG in women and polymorphisms in endothelial nitric oxide synthase, a gene receptive to estrogen regulation, are associated with glaucoma. The study concluded that increasing evidence suggests that lifetime exposure to estrogen may alter the pathogenesis of glaucoma. Estrogen exposure may have a neuroprotective effect on the progression of POAG but further studies need to confirm this finding. The role of sex-specific preventive and therapeutic treatment may be on the horizon.
Topics: Estrogen Replacement Therapy; Estrogens; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Menopause; Optic Nerve Diseases; Pregnancy
PubMed: 26959139
DOI: 10.3109/08820538.2015.1114845 -
International Journal of Molecular... Feb 2021Reactive oxygen species (ROS) plays a key role in the pathogenesis of primary open-angle glaucoma (POAG), a chronic neurodegenerative disease that damages the trabecular... (Review)
Review
Reactive oxygen species (ROS) plays a key role in the pathogenesis of primary open-angle glaucoma (POAG), a chronic neurodegenerative disease that damages the trabecular meshwork (TM) cells, inducing apoptosis of the retinal ganglion cells (RGC), deteriorating the optic nerve head, and leading to blindness. Aqueous humor (AH) outflow resistance and intraocular pressure (IOP) elevation contribute to disease progression. Nevertheless, despite the existence of pharmacological and surgical treatments, there is room for the development of additional treatment approaches. The following review is aimed at investigating the role of different microRNAs (miRNAs) in the expression of genes and proteins involved in the regulation of inflammatory and degenerative processes, focusing on the delicate balance of synthesis and deposition of extracellular matrix (ECM) regulated by chronic oxidative stress in POAG related tissues. The neutralizing activity of a couple of miRNAs was described, suggesting effective downregulation of pro-inflammatory and pro-fibrotic signaling pathways, including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), transforming growth factor-beta 2 (TGF-β2), Wnt/β-Catenin, and PI3K/AKT. In addition, with regards to the elevated IOP in many POAG patients due to increased outflow resistance, Collagen type I degradation was stimulated by some miRNAs and prevented ECM deposition in TM cells. Mitochondrial dysfunction as a consequence of oxidative stress was suppressed following exposure to different miRNAs. In contrast, increased oxidative damage by inhibiting the mTOR signaling pathway was described as part of the action of selected miRNAs. Summarizing, specific miRNAs may be promising therapeutic targets for lowering or preventing oxidative stress injury in POAG patients.
Topics: Animals; Apoptosis; Aqueous Humor; Glaucoma, Open-Angle; Humans; Intraocular Pressure; MicroRNAs; Oxidative Stress; Signal Transduction; Trabecular Meshwork
PubMed: 33670885
DOI: 10.3390/ijms22052421 -
Eye (London, England) Aug 2021To determine the efficacy and safety of combined phacoemulsification and single first-generation iStent implantation over 84 months.
OBJECTIVES
To determine the efficacy and safety of combined phacoemulsification and single first-generation iStent implantation over 84 months.
SUBJECTS/METHODS
Single-surgeon, single-centre, uncontrolled prospective interventional study in real-world settings. Forty-one patients with open-angle glaucoma on at least one antihypertensive drop underwent phaco-iStent surgery. This cohort was monitored over the subsequent 84 months. The primary outcome measure was intraocular pressure (IOP). Secondary outcome measures were number of glaucoma drops, visual acuity, cup-disc-ratio (CDR), mean deviation (MD) and visual field index (VFI). Thirty-one (76%) patients survived to 48 months and 19 (46%) patients to 84 months.
RESULTS
At 84 months, we demonstrate an absolute mean reduction of 4.87 mmHg (95% CI 1.62-7.64) for IOP and 0.59 (95% CI 0.03-1.16) for number of glaucoma drops. At the final clinic visit, LogMAR VA improved by 0.21 (95% CI 0.08-0.34), with no significant change in CDR, MD and VFI. Attrition was mainly due to death (27%) and further glaucoma surgery (12%). A single patient suffered from postoperative hyphaema, with no sequalae. Patients at high risk for progression to filtration surgery were defined as those on oral acetazolamide for IOP control, or those fulfilling all the following criteria: IOP ≥ 20 mmHg, CDR ≥ 0.7, MD ≤ -4.0 dB, number of drops ≥ 2. This group is to be considered for surgery as the next step in management according to NICE glaucoma guidelines. These patients (n = 14) demonstrated a more marked final IOP reduction of 6.85 mmHg (95% CI 3.97-9.75) vs 1.62 mmHg (95% CI 0.04-3.22) in their low-risk counterparts (n = 27). Reduction in glaucoma drops was 0.86 (95% CI 0.07-1.64) for the high-risk and 0.56 (95% CI 0.06-1.05) for the low-risk cohort. Further glaucoma surgery was required for 4 (29%) high-risk and 1 (0.5%) low-risk patients over the study period.
CONCLUSIONS
Our results strongly suggest that the expected outcome of phaco-iStent surgery is a maintained reduction in intraocular pressure and number of glaucoma medications over 7 years. This is combined with a negligible rate of complications, a sustained improvement in central visual acuity, and a reliable maintenance of peripheral visual function.
Topics: Glaucoma, Open-Angle; Humans; Intraocular Pressure; Phacoemulsification; Prospective Studies; Tonometry, Ocular
PubMed: 33139875
DOI: 10.1038/s41433-020-01255-6 -
BMJ Case Reports Apr 2022We report a case of a man in his 50s who developed open-angle glaucoma following neodymium-doped yttrium aluminium garnet (YAG) laser vitreolysis. Despite attempts to...
We report a case of a man in his 50s who developed open-angle glaucoma following neodymium-doped yttrium aluminium garnet (YAG) laser vitreolysis. Despite attempts to control the pressure with topical medication and selective laser trabeculoplasty (SLT), surgical intervention using a Baerveldt glaucoma valve (BGV) was needed after which the intraocular pressure was controlled successfully. This rare but serious complication highlights the fact that in certain cases long-term monitoring of intraocular pressure is necessary following laser vitreolysis.
Topics: Aluminum; Glaucoma, Open-Angle; Humans; Lasers, Solid-State; Male; Trabeculectomy; Yttrium
PubMed: 35487647
DOI: 10.1136/bcr-2022-248937 -
Ceska a Slovenska Oftalmologie :... 2022Mutations in the myocilin gene (MYOC) cause trabecular dysfunction and thus are involved in the pathogenesis of primary open-angle glaucoma (POAG). The aim of this study...
AIM
Mutations in the myocilin gene (MYOC) cause trabecular dysfunction and thus are involved in the pathogenesis of primary open-angle glaucoma (POAG). The aim of this study was to characterize and describe the clinical findings in two Czech families with POAG due to pathogenic variants in the MYOC gene.
MATERIAL AND METHODS
Members of the two families affected by POAG underwent complete ophthalmological examination. In the proband from the first family, a direct sequencing of the three most frequent mutations in the MYOC gene was performed, and in the proband from the second family, an exome sequencing was performed. Other family members underwent targeted tests using direct sequencing.
RESULTS
In total, 10 individuals diagnosed with POAG aged 20-70 years (mean 32.2 years, SD ±10,9 years) were examined. Eight of them showed advanced glaucomatous neuropathy with severe changes in the retinal nerve fiber layer. Clinical signs of POAG were present in six individuals in the third decade of life already; another four developed POAG during the fourth decade of life. Eight out of 10 patients had to undergo filtration surgery. Surgery was performed within 1 to 7 years of diagnosis, but mostly was performed within 2 years of glaucoma diagnosis. In the first family, MYOC variant c.1099G>A p.(Gly367Arg) was shown in the affected family members; in the second family MYOC variant c.1440C>A p.(Asn480Lys), both in heterozygous state. The changes were assessed as pathogenic.
CONCLUSION
Our study is the first to describe mutations in the MYOC gene causing POAG in Czech patients. Genetic testing may be recommended for this diagnosis, especially in individuals with early presentation and a positive family history. Carriers of pathogenic variants of the MYOC gene have a lifetime risk of developing POAG of more than 50% and the course of their disease is often more aggressive, requiring surgical intervention to permanently control the intraocular pressure.
Topics: Eye Proteins; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Mutation; Pedigree
PubMed: 36220364
DOI: 10.31348/2022/25 -
BMC Ophthalmology Sep 2023This systematic review and meta-analysis summarize the evidence for the association between Helicobacter pylori infection and Primary Open-Angle Glaucoma. (Meta-Analysis)
Meta-Analysis
PURPOSE
This systematic review and meta-analysis summarize the evidence for the association between Helicobacter pylori infection and Primary Open-Angle Glaucoma.
METHODS
Eligible studies reporting an association between H. pylori infection and Glaucoma were identified through an extensive search of the Excerpta Medica (EMBASE), Web of Science, Scopus, and PubMed databases and an assessment of the reference list of the top articles until October 2022. Analysis was performed with random effects model using Stata 16.
RESULT
Twenty-four studies were included in the systematic review. This study involved 1602 glaucoma patients and 2800 control individuals. The combined RRs of cohort studies and overall combined ORs of case-control studies showed a significant correlation between H. pylori infection and Glaucoma. Subgroup analysis showed that glaucoma patients had a higher risk of having H. pylori infection if they were residents of Europe countries (Cohort: RR: 1.69; 95% CI: 1.3-2.19) and (Case-Control: RR: 3.71; 95% CI: 2.07-6.64), if they had POAG type (Cohort: RR: 1.76; 95% CI: 1.37-2.27) and (Case-Control: RR: 3.71; 95% CI: 2.934.70), if their diagnostic method of HP was histology (Cohort: RR: 1.95; 95% CI: 1.26-3.01) and (Case-Control: RR: 4.06; 95% CI: 2.28-7.22), and if they were over 60 years old (Cohort: RR: 1.63; 95% CI: 1.33-2.00) and (Case-Control: RR: 2.95; 95% CI: 2.27-3.83).
DISCUSSION
The results of this meta-analysis suggest a statistically significant association between Helicobacter pylori infection and Primary Open-Angle Glaucoma.
Topics: Humans; Middle Aged; Helicobacter Infections; Glaucoma, Open-Angle; Helicobacter pylori; Case-Control Studies; Glaucoma
PubMed: 37697285
DOI: 10.1186/s12886-023-03111-z