-
Scientific Reports Jun 2023Primary open angle glaucoma (POAG) is a chronic, adult-onset optic neuropathy associated with characteristic optic disc and/or visual field changes. With a view to...
Primary open angle glaucoma (POAG) is a chronic, adult-onset optic neuropathy associated with characteristic optic disc and/or visual field changes. With a view to identifying modifiable risk factors for this common neurodegenerative condition, we performed a 'phenome-wide' univariable Mendelian randomisation (MR) study that involved analysing the relationship between 9661 traits and POAG. Utilised analytical approaches included weighted mode based estimation, the weighted median method, the MR Egger method and the inverse variance weighted (IVW) approach. Eleven traits related to POAG risk were identified including: serum levels of the angiopoietin-1 receptor (OR [odds ratio] = 1.11, IVW p = 2.34E-06) and the cadherin 5 protein (OR = 1.06, IVW p = 1.31E-06); intraocular pressure (OR = 2.46-3.79, IVW p = 8.94E-44-3.00E-27); diabetes (OR = 5.17, beta = 1.64, IVW p = 9.68E-04); and waist circumference (OR = 0.79, IVW p = 1.66E-05). Future research focussing on the effects of adiposity, cadherin 5 and angiopoietin-1 receptor on POAG development and progression is expected to provide key insights that might inform the provision of lifestyle modification advice and/or the development of novel therapies.
Topics: Adult; Humans; Angiopoietin-1; Glaucoma, Open-Angle; Causality; Phenomics; Phenotype; Mendelian Randomization Analysis; Genome-Wide Association Study; Polymorphism, Single Nucleotide
PubMed: 37340071
DOI: 10.1038/s41598-023-37144-7 -
Romanian Journal of Ophthalmology 2021Ultrasound biomicroscopy (UBM) is an important tool in the diagnosis, evaluation and follow up of glaucoma patients. Even if we are dealing with a primary angle closure... (Review)
Review
Ultrasound biomicroscopy (UBM) is an important tool in the diagnosis, evaluation and follow up of glaucoma patients. Even if we are dealing with a primary angle closure glaucoma (PACG) or a primary open angle glaucoma (POAG) patient, the mechanism of angle closure can be revealed by performing an UBM. The device can help differentiate between the two types of glaucoma even in patients with opaque corneas when gonioscopy cannot be performed. Knowing the type of glaucoma is vital, especially regarding an individualized treatment, since each patient is unique and needs to be treated accordingly, in order to prevent glaucomatous optic neuropathy and visual field loss. : AC = anterior chamber, ICE = iridocorneal endothelial syndrome, IOP = intraocular pressure, NTG = normal tension glaucoma, PACG = primary angle closure glaucoma, PC = posterior chamber, PEX = pseudoexfoliation syndrome, POAG = primary open angle glaucoma, UBM = ultrasound biomicroscopy.
Topics: Glaucoma, Angle-Closure; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Microscopy, Acoustic; Tonometry, Ocular; Visual Fields
PubMed: 34179574
DOI: 10.22336/rjo.2021.24 -
Turkish Journal of Ophthalmology Aug 2023Pseudoexfoliation syndrome (PES) is one of the most common causes of open-angle glaucoma, with a higher risk of vision loss, a higher maximum and mean intraocular... (Review)
Review
Pseudoexfoliation syndrome (PES) is one of the most common causes of open-angle glaucoma, with a higher risk of vision loss, a higher maximum and mean intraocular pressure (IOP) at diagnosis, and a wider range of IOP fluctuation compared to primary open-angle glaucoma. Patients with this syndrome have a ten-fold higher risk of developing glaucoma than the normal population. A definite diagnosis can be made by the observation of pseudoexfoliation material (PEM) on the anterior lens surface, ciliary processes, zonules, and iris. PEM deposits on the zonules may explain the clinically observed zonular weakness and lens subluxation or dislocation. An increased incidence of cataract development is also associated with PES. There is growing evidence for systemic associations of PES with peripheral, cardiovascular, and cerebrovascular system diseases, Alzheimer's disease, hearing loss, and increased plasma homocysteine levels. Indications for surgery are markedly more common in patients with pseudoexfoliation glaucoma than primary open-angle glaucoma. The goal of this article is to review the latest perspectives on the clinical features, therapy, and systemic associations of this clinically and biologically challenging disease.
Topics: Humans; Cataract; Exfoliation Syndrome; Glaucoma; Glaucoma, Open-Angle; Lens Subluxation
PubMed: 37602651
DOI: 10.4274/tjo.galenos.2023.76300 -
Journal of Translational Medicine Nov 2023In primary open-angle glaucoma (POAG), lowering intraocular pressure (IOP) is the only proven way of slowing vision loss. Schlemm's canal (SC) is a hybrid vascular and...
BACKGROUND
In primary open-angle glaucoma (POAG), lowering intraocular pressure (IOP) is the only proven way of slowing vision loss. Schlemm's canal (SC) is a hybrid vascular and lymphatic vessel that mediates aqueous humour drainage from the anterior ocular chamber. Animal studies support the importance of SC endothelial angiopoietin-TEK signalling, and more recently TIE1 signalling, in maintaining normal IOP. However, human genetic support for a causal role of TIE1 and TEK signalling in lowering IOP is currently lacking.
METHODS
GWAS summary statistics were obtained for plasma soluble TIE1 (sTIE1) protein levels (N = 35,559), soluble TEK (sTEK) protein levels (N = 35,559), IOP (N = 139,555) and POAG (N = 16,677, N = 199,580). Mendelian randomization (MR) was performed to estimate the association of genetically proxied TIE1 and TEK protein levels with IOP and POAG liability. Where significant MR estimates were obtained, genetic colocalization was performed to assess the probability of a shared causal variant (PP) versus distinct (PP) causal variants underlying TIE1/TEK signalling and the outcome. Publicly available single-nucleus RNA-sequencing data were leveraged to investigate differential expression of TIE1 and TEK in the human ocular anterior segment.
RESULTS
Increased genetically proxied TIE1 signalling and TEK signalling associated with a reduction in IOP (- 0.21 mmHg per SD increase in sTIE1, 95% CI = - 0.09 to - 0.33 mmHg, P = 6.57 × 10, and - 0.14 mmHg per SD decrease in sTEK, 95% CI = - 0.03 to - 0.25 mmHg, P = 0.011), but not with POAG liability. Colocalization analysis found that the probability of a shared causal variant was greater for TIE1 and IOP than for TEK and IOP (PP/(PP + PP) = 0.98 for TIE1 and 0.30 for TEK). In the anterior segment, TIE1 and TEK were preferentially expressed in SC, lymphatic, and vascular endothelium.
CONCLUSIONS
This study provides novel human genetic support for a causal role of both TIE1 and TEK signalling in regulating IOP. Here, combined evidence from cis-MR and colocalization analyses provide stronger support for TIE1 than TEK as a potential IOP-lowering therapeutic target.
Topics: Animals; Humans; Intraocular Pressure; Glaucoma, Open-Angle; Mendelian Randomization Analysis; Angiopoietins
PubMed: 37996923
DOI: 10.1186/s12967-023-04737-9 -
Journal of Clinical Sleep Medicine :... May 2023
Topics: Humans; Glaucoma, Open-Angle; Sleep Apnea, Obstructive; Prevalence
PubMed: 36747486
DOI: 10.5664/jcsm.10494 -
PloS One 2023To evaluate the short-term clinical outcomes of microincisional trabeculectomy (MIT), a new technique of ab-interno trabeculectomy.
PURPOSE
To evaluate the short-term clinical outcomes of microincisional trabeculectomy (MIT), a new technique of ab-interno trabeculectomy.
METHODS
Consecutive patients with open-angle glaucoma identified from the hospital database that underwent MIT with or without cataract surgery between September 2021 to June 2022 at a tertiary eye centre in East India, were screened. Those with a follow-up of < 6 months or with incomplete data were excluded. MIT was done ab-interno using microscissors and microforceps in 2-4 clock hours of the nasal angle via a temporal incision. The intraocular pressure (IOP) reduction at 6 months, and reduction in the number of medications after surgery were analysed. Surgical success (IOP>6 and <22 mm Hg), complications, angle features on anterior segment optical coherence tomography (ASOCT), and the need for additional surgeries were analysed.
RESULTS
We included thirty-two eyes of 32 patients with open-angle glaucoma (including n = 9 eyes that underwent concurrent cataract surgery) with a preoperative mean IOP of 22 ±11.1 mm Hg and visual field index of 47±37.9%. All eyes achieved >30% IOP reduction, with a final IOP of 14±6.9 mm Hg at 6 months. Surgical success in 31 of 32 eyes with complete success seen in 28 eyes with none of the eyes requiring >1 medication for IOP control. Hyphema was seen in 4 eyes, while transient IOP spikes at 1 day-1 month were seen in 5 eyes, none of which required any additional interventions. One eye with persistent raised IOP at 1 month required incisional trabeculectomy for uncontrolled IOP with 2 medications.
CONCLUSION
MIT, a new technique of ab-interno trabeculectomy, is effective in terms of IOP control and reduction in the number of medications while having fewer complications. Long-term studies comparing the efficacy of MIT with incisional trabeculectomy, or other procedures are warranted in the future.
Topics: Humans; Glaucoma, Open-Angle; Intraocular Pressure; Treatment Outcome; Glaucoma; Cataract; Retrospective Studies; Follow-Up Studies
PubMed: 37205654
DOI: 10.1371/journal.pone.0286020 -
Drugs & Aging Jun 2020Bimatoprost implant (Durysta™), developed by Allergan, is a sustained-release drug delivery system containing bimatoprost, a prostaglandin analogue with ocular... (Review)
Review
Bimatoprost implant (Durysta™), developed by Allergan, is a sustained-release drug delivery system containing bimatoprost, a prostaglandin analogue with ocular hypotensive activity. The implant, administered intracamerally, involves the use of a biodegradable, solid polymer drug delivery system for slow, sustained drug release, designed to lower intraocular pressure (IOP) over a 4- to 6-months period. In March 2020, bimatoprost implant received its first approval, in the USA, for use to reduce IOP in patients with open angle glaucoma (OAG) or ocular hypertension (OHT). Allergan's clinical development programme for bimatoprost implant is ongoing. This article summarizes the milestones in the development of bimatoprost implant leading to this first approval for use in the reduction of IOP in patients with OAG or OHT.
Topics: Bimatoprost; Drug Approval; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Ocular Hypertension; Prostheses and Implants
PubMed: 32447639
DOI: 10.1007/s40266-020-00769-8 -
Experimental Eye Research Jun 2022Glaucoma is a heterogeneous group of progressive optic neurodegenerative. Although most patients with primary open angle glaucoma (POAG) are stable for many years,...
Glaucoma is a heterogeneous group of progressive optic neurodegenerative. Although most patients with primary open angle glaucoma (POAG) are stable for many years, certain subgroups of POAG patients could progress over time even with treatment. This study is to identify aqueous humor (AH) biomarkers that may be associated with disease progression in POAG patients. Gene differential expression study of prospectively collected AH from patients with stable or progressive POAG. Metagenomic deep sequencing (MDS) was performed on the aqueous fluid of 20 patients with stable POAG and 20 patients with progressive POAG. Differential gene expression analysis was performed to identify host transcriptome signatures. A total of 21 transcripts were differentially expressed between groups. Differential transcripts identified by MDS. Twenty transcripts were up-regulated and 1 transcript was down-regulated in progressive POAG patients compared to stable patients. Of those, 11 transcripts were eye-related, and 5 transcripts were related to glaucomatous phenotypes (Fibronectin type III domain containing 3B (FNDC3B), Clusterin (CLU), Proprotein convertase subtilisin/kexin type 6 (PCSK6), Cadherin EGF LAG seven-pass G-type receptor 1 (Celsr1), and Rho guanine nucleotide exchange factor 4 (ARHGEF4)). Biomarkers associated with POAG progression can be identified from aqueous fluid. Identification of the biomarkers may improve glaucoma surveillance for progressive POAG.
Topics: Aqueous Humor; Biomarkers; Eye; Glaucoma; Glaucoma, Open-Angle; Humans; Rho Guanine Nucleotide Exchange Factors
PubMed: 35278478
DOI: 10.1016/j.exer.2022.109025 -
BMC Ophthalmology Feb 2020The primary aim was to estimate the incidence of primary and secondary childhood glaucoma in Scotland over a 2-year period. The secondary aim was to gauge the confidence...
BACKGROUND
The primary aim was to estimate the incidence of primary and secondary childhood glaucoma in Scotland over a 2-year period. The secondary aim was to gauge the confidence and experience of ophthalmologists in Scotland in managing these patients.
METHODS
A 7 question electronic survey was distributed to all consultant members of the Scottish Paediatric Club and Scottish Glaucoma Club. Respondents were asked to report the number of cases and types of childhood glaucoma they had managed in the last 2 years. Respondents were also asked about experience and confidence in a range of glaucoma procedures, number of patients requiring referral to specialist centres and interest in the development of a centre of excellence in Scotland.
RESULTS
The survey returned a 56% response rate, reporting 85 new cases of paediatric glaucoma in Scotland over the preceding 2 years. 11 (12.9%) had primary glaucoma and 74 (87.1%) had secondary glaucoma. The most common subtype of secondary glaucoma was uveitic glaucoma (n = 29). None of the respondents declared confidence or experience in trabeculotomy or goniotomy procedures. Eleven children required referral to a specialist unit outside Scotland. 85.7% of respondents felt Scotland would benefit from a specialist unit for paediatric glaucoma.
CONCLUSIONS
This survey reflects an appetite for a specialist service for paediatric glaucoma in Scotland. However, further consideration is needed to determine if there is sufficient patient load to maintain such a service.
Topics: Child; Child, Preschool; Female; Glaucoma Drainage Implants; Glaucoma, Open-Angle; Health Surveys; Humans; Hydrophthalmos; Incidence; Intraocular Pressure; Male; Practice Patterns, Physicians'; Referral and Consultation; Scotland; Surveys and Questionnaires; Trabeculectomy
PubMed: 32103740
DOI: 10.1186/s12886-020-01347-7 -
Journal of Neuroinflammation Jul 2023Dysfunction of microglia during aging affects normal neuronal function and results in the occurrence of neurodegenerative diseases. Retinal microglial senescence...
BACKGROUND
Dysfunction of microglia during aging affects normal neuronal function and results in the occurrence of neurodegenerative diseases. Retinal microglial senescence attributes to retinal ganglion cell (RGC) death in glaucoma. This study aims to examine the role of ATP-P2XR in the mediation of microglia senescence and glaucoma progression.
METHODS
Forty-eight participants were enrolled, including 24 patients with primary open-angle glaucoma (POAG) and age-related cataract (ARC) and 24 patients with ARC only. We used ARC as the inclusion criteria because of the availability of aqueous humor (AH) before phacoemulsification. AH was collected and the adenosine triphosphate (ATP) concentration was measured by ATP Assay Kit. The chronic ocular hypertension (COH) mouse model was established by microbead occlusion. Microglia were ablated by feeding PLX5622 orally. Mouse bone marrow cells (BMCs) were prepared and infused into mice through the tail vein for the restoration of microglia function. Western blotting, qPCR and ELISA were performed to analyze protein and mRNA expression in the ocular tissue, respectively. Microglial phenotype and RGC survival were assessed by immunofluorescence. The mitochondrial membrane potential was measured using a JC-1 assay kit by flow cytometry.
RESULTS
ATP concentrations in the AH were increased in older adults and patients with POAG. The expression of P2XR was upregulated in the retinal tissues of mice with glaucoma, and functional enrichment analysis showed that P2XR was closely related to cell aging. Through in vivo and in vitro approaches, we showed that pathological activation of ATP-P2XR induced accelerated microglial senescence through impairing PTEN-induced kinase 1 (PINK1)-mediated mitophagy, which led to RGC damage. Additionally, we found that replacement of senescent microglia in COH model of old mice with BMCs from young mice reversed RGC damage.
CONCLUSION
ATP-P2XR induces microglia senescence by inhibiting PINK1-mediated mitophagy pathway. Specific inhibition of ATP-P2XR may be a fundamental approach for targeted therapy of RGC injury in microglial aging-related glaucoma.
Topics: Mice; Animals; Retinal Ganglion Cells; Microglia; Adenosine Triphosphate; Glaucoma, Open-Angle; Ocular Hypertension; Glaucoma; Disease Models, Animal; Protein Kinases
PubMed: 37525172
DOI: 10.1186/s12974-023-02855-1