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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 -
Asia-Pacific Journal of Ophthalmology... 2016Selective laser trabeculoplasty (SLT) is an effective treatment option for the reduction of intraocular pressure (IOP) in patients with ocular hypertension or open-angle... (Review)
Review
Selective laser trabeculoplasty (SLT) is an effective treatment option for the reduction of intraocular pressure (IOP) in patients with ocular hypertension or open-angle glaucoma. The mechanism by which SLT lowers IOP is not completely understood and is likely multifactorial. Published studies indicate that SLT is at least as effective as argon laser trabeculoplasty or medications at lowering IOP in many forms of glaucoma. In addition to IOP reduction, SLT may decrease IOP fluctuation and can be successfully used as primary or adjunctive therapy for the management of both early and advanced glaucoma. However, SLT may not be effective in certain forms of glaucoma, and the IOP-lowering effect seems to wane with time. High pretreatment IOP is the strongest predictor of treatment success, even in patients with normal-tension glaucoma. Repeatability of SLT has been controversial, but recent evidence suggests that it can be successfully repeated to achieve additional or recurrent IOP reduction, even in eyes that only had a modest response to initial treatment. Adverse events are uncommon after SLT, and the most common complications such as discomfort and inflammation are typically mild and transient. Further investigation is required to determine the optimal treatment parameters for SLT treatment. Limited evidence suggests that SLT is cost-effective as primary therapy for patients with glaucoma.
Topics: Glaucoma, Open-Angle; Humans; Intraocular Pressure; Laser Therapy; Ocular Hypertension; Trabeculectomy
PubMed: 26886122
DOI: 10.1097/APO.0000000000000175 -
Investigative Ophthalmology & Visual... Dec 2022To investigate the association of systemic blood pressure and incident primary open-angle glaucoma (POAG) using a large open-access database.
PURPOSE
To investigate the association of systemic blood pressure and incident primary open-angle glaucoma (POAG) using a large open-access database.
METHODS
Prospective cohort study included 484,268 participants from the UK Biobank without glaucoma at enrollment. Incident POAG events were recorded through assessment visits, hospital inpatient admissions, and primary care data. Blood pressure measures included systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), and mean arterial pressure (MAP). Repeated measurements throughout the study period were analyzed as time-varying covariables. The parameters were modeled as both categorical and continuous nonlinear variables. The primary outcome measure was the relative hazard of incident POAG.
RESULTS
There were 2390 incident POAG events over 5,715,480 person-years of follow-up. Median follow-up was 12.08 years. In multivariable analyses, compared to SBP and PP in the normal range (SBP, 120-130 mmHg; PP, 40-50 mmHg), higher SBP and PP were associated with an increased risk of incident POAG (linear trend P = 0.038 for SBP, P < 0.001 for PP). Specifically, SBP of 130 to 140 mmHg or 140 to 150 mmHg was associated with a 1.16 higher hazard of incident POAG (95% CI, 1.01-1.32 and 1.01-1.33, respectively), whereas a PP of greater than 70 mmHg was associated with a 1.13 higher hazard of incident glaucoma (95% CI, 1.00-1.29). In multivariable models, no statistically significant associations were found for DBP or MAP with incident glaucoma. These findings were similar when blood pressure measures were modeled as continuous variables.
CONCLUSIONS
Higher SBP and PP were associated with an increased risk of incident POAG. Further studies are required to characterize these relationships better.
Topics: Humans; Blood Pressure; Glaucoma, Open-Angle; Prospective Studies; Arterial Pressure; Risk Factors
PubMed: 36469027
DOI: 10.1167/iovs.63.13.3 -
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 -
Eye (London, England) Nov 2022To estimate the risk of blindness with primary angle-closure glaucoma (PACG) compared to primary open-angle glaucoma (POAG) in those population-based studies that... (Meta-Analysis)
Meta-Analysis
AIM
To estimate the risk of blindness with primary angle-closure glaucoma (PACG) compared to primary open-angle glaucoma (POAG) in those population-based studies that reported blindness rates for both PACG and POAG.
METHOD
A systematic search was performed in PubMed for articles published in English between 2000 and 2020 reporting the prevalence of POAG as well as PACG among various ethnic populations. A study was included if it was (1) population-based (2) had published prevalence and blindness rates for both PACG and POAG in the same cohort. (3) Glaucoma was defined as per the International Society for Geographical and Epidemiological Ophthalmology (ISGEO) criteria. The proportion of blindness for both POAG and PACG for each study and the cumulative proportion taking all the studies were calculated.
RESULTS
We included 23 studies with 78,434 participants. POAG was diagnosed in 1702 persons with 151 (8.9%) blind. There were 724 cases of PACG with 196 (27.0%) blind. The risk ratio of blindness in PACG to POAG varied from 0.73 to 10.6 among the studies. The cumulative risk ratio was 2.39 (95% confidence interval (CI); 1.99, 2.87). Risk ratios for studies including visual field restriction while defining blindness were similar to studies that did not (1.92 vs 2.64, P = 0.11). Risk ratios were also similar for studies that used greater than 2 instead of 3 or more quadrants of iridotrabecular contact to define angle closure (2.79 vs 2.25).
CONCLUSION
Primary angle-closure disease is more likely to be associated with blindness.
Topics: Humans; Blindness; Glaucoma; Glaucoma, Angle-Closure; Glaucoma, Open-Angle; Intraocular Pressure; Visual Field Tests
PubMed: 34645961
DOI: 10.1038/s41433-021-01802-9