Genetic Determinants of Intraocular Pressure

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Zihe Xu ◽  
Pirro Hysi ◽  
Anthony P. Khawaja
Keyword(s):  
Intraocular Pressure ◽  
Primary Open Angle Glaucoma ◽  
Open Angle Glaucoma ◽  
Association Studies ◽  
Characteristic Curve ◽  
Annual Review ◽  
Publication Date ◽  
Genome Wide Association Studies ◽  
Open Angle ◽  
Vision Science

Intraocular pressure (IOP) is the cardinal and only modifiable risk factor for glaucoma, the leading cause of irreparable blindness worldwide. Twin and family studies estimate the heritability of IOP to be 40–70%, and linkage studies for IOP have identified numerous loci. Mutations in MYOC can cause markedly elevated IOP and aggressive glaucoma often requiring surgical intervention. However, the majority of the genetic basis for raised IOP and glaucoma in populations is complex, and recent large genome-wide association studies (GWASs) have identified over 100 common variants that contribute to IOP variation. In combination, these loci are predictive for primary open-angle glaucoma in independent populations, achieving an area under the receiver operating characteristic curve of 76% for high-pressure primary open-angle glaucoma; this suggests the possibility of targeted screening in the future. Additionally, GWAS findings have identified important biological pathways underlying IOP regulation, including lymphangiogenesis and lipid metabolism, providing novel targets for new therapies. Expected final online publication date for the Annual Review of Vision Science, Volume 7 is September 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals CDKN2B-AS1 gene polymorphism is associated with primary open-angle glaucoma in women of the Central Black Earth Region, Russia

2021 ◽  
Author(s):  
NV Eliseeva ◽  
IV Ponomarenko ◽  
MI Churnosov
Keyword(s):  
Gene Polymorphism ◽  
Protective Factor ◽  
Haplotype Block ◽  
Primary Open Angle Glaucoma ◽  
Open Angle Glaucoma ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Open Angle ◽  
Genome Wide

Primary open-angle glaucoma (POAG) is a complex disorder. Genetic factors play a vital part in POAG. The prevalence of POAG is gender-specific: the disorder is more often diagnosed in women. Results of the genome-wide association studies (GWAS) strongly support the association of CDKN2B-AS1 gene polymorphism with POAG. The aim was to perform the replicative study of CDKN2B-AS1 gene polymorphic loci association with POAG in women of the Central Black Earth Region, Russia. Five CDKN2B-AS1 gene single nucleotide polymorphisms (SNP), rs1063192, rs7865618, rs2157719, rs944800, and rs4977756, were genotyped in 290 female patients with POAG and 220 female controls. The differences in the haplotype block structure between the POAG patients (no haplotype blocks) and the controls (haplotype block consisting of three SNPs, rs1063192, rs7865618 and rs2157719, was detected) for the set of studied CDKN2B-AS1 SNPs were revealed using the Solid Spine algorithm (D’ > 0.8). CDKN2B-AS1 gene haplotype GGG rs1063192–rs7865618–rs2157719 is associated with POAG in women. This haplotype is considered a protective factor of the disorder (OR = 0.66; p = 0.006, рperm = 0.037).

scholarly journals A large cross-ancestry meta-analysis of genome-wide association studies identifies 69 novel risk loci for primary open-angle glaucoma and includes a genetic link with Alzheimer’s disease

2020 ◽  
Author(s):  
Puya Gharahkhani ◽  
Eric Jorgenson ◽  
Pirro Hysi ◽  
Anthony P. Khawaja ◽  
Sarah Pendergrass ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Primary Open Angle Glaucoma ◽  
Open Angle Glaucoma ◽  
Association Studies ◽  
Meta Analysis ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Open Angle ◽  
Risk Genes ◽  
Genome Wide

AbstractWe conducted a large multi-ethnic meta-analysis of genome-wide association studies for primary open-angle glaucoma (POAG) on a total of 34,179 cases vs 349,321 controls, and identified 127 independent risk loci, almost doubling the number of known loci for POAG. The majority of loci have broadly consistent effect across European, Asian and African ancestries. We identify a link, both genome-wide and at specific loci, between POAG and Alzheimer’s disease. Gene expression data and bioinformatic functional analyses provide further support for the functional relevance of the POAG risk genes. Several drug compounds target these risk genes and may be potential candidates for developing novel POAG treatments.

scholarly journals Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Puya Gharahkhani ◽  
◽  
Eric Jorgenson ◽  
Pirro Hysi ◽  
Anthony P. Khawaja ◽  
...  
Keyword(s):  
Primary Open Angle Glaucoma ◽  
Open Angle Glaucoma ◽  
Association Studies ◽  
Meta Analysis ◽  
Genome Wide Association Studies ◽  
Open Angle ◽  
Risk Genes ◽  
Genome Wide ◽  
Causal Variants ◽  
Functional Relevance

AbstractPrimary open-angle glaucoma (POAG), is a heritable common cause of blindness world-wide. To identify risk loci, we conduct a large multi-ethnic meta-analysis of genome-wide association studies on a total of 34,179 cases and 349,321 controls, identifying 44 previously unreported risk loci and confirming 83 loci that were previously known. The majority of loci have broadly consistent effects across European, Asian and African ancestries. Cross-ancestry data improve fine-mapping of causal variants for several loci. Integration of multiple lines of genetic evidence support the functional relevance of the identified POAG risk loci and highlight potential contributions of several genes to POAG pathogenesis, including SVEP1, RERE, VCAM1, ZNF638, CLIC5, SLC2A12, YAP1, MXRA5, and SMAD6. Several drug compounds targeting POAG risk genes may be potential glaucoma therapeutic candidates.

Clinical efficacy of osteopathic correction in the complex treatment of patients with unoperated open-angle glaucoma

2020 ◽  
pp. 97-105
Author(s):  
E. N. Simakova ◽  
O. V. Stenkova
Keyword(s):  
Intraocular Pressure ◽  
Drug Therapy ◽  
Primary Open Angle Glaucoma ◽  
Open Angle Glaucoma ◽  
Randomized Study ◽  
Main Group ◽  
Control Group ◽  
Open Angle ◽  
Complex Treatment ◽  
Hypotensive Drug

Introduction. Glaucoma is one of the most significant eye diseases. It is often diagnosed, not always amenable to therapy, and can lead to a complete loss of visual functions. In recent years, the method of osteopathic correction has become widespread as one of the effective methods of treatment and rehabilitation of patients with pathologies of various body systems. In the pathogenesis of glaucoma, it is customary to distinguish a dystrophic concept, which considers primary open-angle glaucoma as a result of dystrophic changes in the connective tissue, as well as in the endothelial lining of the trabeculae and Schlemm′s canal, especially destructive changes in mitochondria and the alteration of their functional activity. A vascular concept is also distinguished. According to this concept, the central link in the pathogenesis of glaucoma is circulatory disorder in the ciliary vessels, ocular artery, and major vessels of the head and neck, it can be assumed that osteopathic correction in the treatment of patients with open-angle glaucoma will be pathogenetically substantiated and will have a positive effect on intraocular pressure and trophicity of the optic nerve. The goal of research — to study the influence of in osteopathic correction on the nature of unoperated glaucoma (stage IIA) and to substantiate the possibility of using osteopathic correction in the complex treatment of patients with this pathology.Materials and methods. A prospective controlled randomized study was conducted at 52 city polyclinics, branch 3, Moscow, from January 2018 to January 2019. 40 patients (70 eyes) aged 50 to 75 years with primary open-angle glaucoma IIA stage were examined. At this stage of the disease, patients most often seek medical care and the issue of conservative management is primarily considered. All patients were divided into two groups of 20 people: the main group and the control group. The treatment in the main group included hypotensive drug therapy and osteopathic correction. Patients of the control group received only drug therapy. All patients underwent ophthalmic (visometry, tonometry, perimetry) and osteopathic examination twice: before the treatment and after 3 months.Results. For patients with primary open-angle IIA non-operated glaucoma, regional (most often regions of the head, neck, dura mater) and local (abdominal diaphragm, iliac bones, hip and knee joints) somatic dysfunctions were the most typical. In the main group a statistically significant decrease in the frequency and severity of dysfunctions at all levels was stated. Also, in patients receiving osteopathic correction, a significant decrease in the level of intraocular pressure and perimetric indices was noted. In patients of the control group, no reliable changes in these indicators were obtained.Conclusion. The results obtained indicate that osteopathic correction is clinically effective in the complex treatment of patients with primary open-angle II A glaucoma.

scholarly journals Intraocular Pressure-Lowering Potential of Subthreshold Selective Laser Trabeculoplasty in Patients with Primary Open-Angle Glaucoma

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Hong Yang Zhang ◽  
Yong Jie Qin ◽  
Yang Fan Yang ◽  
Jian Gang Xu ◽  
Min Bin Yu
Keyword(s):  
Intraocular Pressure ◽  
Primary Open Angle Glaucoma ◽  
Open Angle Glaucoma ◽  
Initial Energy ◽  
The Other ◽  
Open Angle ◽  
Selective Laser Trabeculoplasty ◽  
Laser Trabeculoplasty ◽  
Pressure Lowering ◽  
Laser Flare

Purpose.To compare the efficacy of subthreshold and conventional selective laser trabeculoplasty (SLT) in lowering intraocular pressure (IOP) in the patients with primary open-angle glaucoma (POAG).Methods.Fifty-two eyes from fifty-two POAG patients were randomized into two groups, one group treated with subthreshold SLT using two-thirds of the conventional energy and the other one treated with the conventional energy. IOP was measured with the Goldmann tonometer and the anterior chamber inflammation was determined using laser flare meter.Results.The initial energy dosage used in subthreshold SLT group was significantly lower than the amount of the energy used in conventional SLT group (0.4±0.1 mJ versus0.6±0.1 mJ,P=0.030). The total energy dosage was also significantly lower in subthreshold SLT group compared to the other group (37.6±3.3 mJ versus51.8±5.7 mJ,P=0.036). However, the level of inflammation in aqueous humor, amount of reduction in IOP, and the success rate in controlling IOP was the same in both groups.Conclusion.The efficacy of subthreshold SLT group in reducing IOP in POAG patients is comparable to the efficacy of conventional SLT group.

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