Retinal vessels change in primary angle-closure glaucoma: the Handan Eye Study.
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ABSTRACT:
SUBMITTER: Gao J
PROVIDER: S-EPMC4415423 | biostudies-other | 2015
REPOSITORIES: biostudies-other
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Project description:PURPOSE:The purpose of this article is to investigate the changes in the retinal vasculature in different parts of the fundus in eyes with primary angle closure glaucoma (PACG). METHODS:Healthy subjects and those with PACG were enrolled. Optical coherence tomography and a split-spectrum amplitude decorrelation angiography algorithm were used to quantify the retinal vessel densities in the parafoveal and peripapillary areas. RESULTS:Thirty-nine eyes from 24 PACG patients and 39 eyes from 20 age-matched and sex-matched healthy subjects were included. The retinal vessel densities in the parafoveal and peripapillary areas and every sector of the 2 areas were significantly lower in the PACG eyes than in the healthy eyes. The difference was greater in the peripapillary area (11.75%) than in the parafoveal area (7.55%, P<0.05). In the PACG eyes, the vessel density in the peripapillary area correlated closely with the intraocular pressure, but that in the parafoveal area did not. When the PACG eyes were divided into groups with well-controlled and not well-controlled intraocular pressure (?21?mm?Hg or not), the vessel density and retinal nerve fiber layer thickness in the peripapillary area were much lower in the not well-controlled eyes (P<0.05), whereas the vessel density in the parafovea and the ganglion cell complex thickness were similar in the 2 subgroups. CONCLUSION:Retinal vessel density was significantly reduced in PACG eyes. The magnitude of this difference varied between the fundus areas, and was greater in the peripapillary area.
| S-EPMC5880710 | biostudies-literature
Project description:Shorter axial length observed in patients with primary angle closure glaucoma (PACG) might be due to altered matrix metalloproteinase-9 (MMP9) activity resulting in ECM remodeling during eye growth and development. This study aimed to evaluate common variants in MMP9 for association with PACG. Six tag SNPs of MMP9 were genotyped in a Chinese sample of 1,030 cases, including 572 PACG and 458 primary angle closure (PAC), and 499 controls. None of 6 SNPs were significantly associated with overall PAC/PACG (P > 0.07) or with PAC/PACG subgroups (Pc > 0.18). Meta-analysis of two non-Chinese studies revealed significant association between rs17576 and PACG (ORs = 0.56, P < 0.0001); however, meta-analysis of our dataset with 4 Chinese datasets did not replicate this association (ORs = 1.23, P = 0.29). Prior significant association for rs3918249 in one Caucasian study (OR = 0.63, P = 0.006) was not replicated in meta-analysis of 3 Chinese studies including this study (ORs = 0.91, P = 0.13). Significant heterogeneity between non-Chinese and Chinese datasets precluded overall meta-analysis for rs17576 and rs3918249 (Q = 0.001 and 0.04 respectively). rs17577 was nominally associated with PACG in one Caucasian study (OR = 1.71, P = 0.02), but not in 3 Chinese studies including our study (ORs = 1.20, P = 0.07). Overall meta-analysis revealed nominal association for rs17577 and PAC/PACG (ORs = 1.26, Pc = 0.05). Meta-analysis did not show significant association between the other SNPs and PAC/PACG (P > 0.47). The largest association study to date did not find significant association between MMP9 and PAC/PACG in Chinese; meta-analysis with other Chinese datasets did not produce significant association. In most instances combination with non-Chinese datasets was not possible except for one variant showing nominally significant association. More work is needed to define the role of MMP9 variants in PACG.
| S-EPMC4896618 | biostudies-literature
Project description:Primary Angle Closure Glaucoma (PACG) is one of the most common types of glaucoma affecting over 15 million individuals worldwide. Family history and ethnicity are strongly associated with the development of the disease, suggesting that one or more genetic factors contribute to PACG. Although strictly heritable disease-causing mutations have not been identified, a number of recent association studies have pointed out genetic factors that appear to contribute to an individual's risk to develop PACG. In addition, genetic factors have been identified that modify PACG endophenotypes for example, axial length. Herein we review the current literature on this important topic.
| S-EPMC4815686 | biostudies-literature
Project description:Genome-wide association study (GWAS) analysis identified three new susceptibility loci for PACG. In this study, we aimed to investigate whether these three loci in PLEKHA7, COL11A1, and PCMTD1-ST18 are associated with PAC and ocular biometric characteristics, such as axial length (AL), anterior chamber depth (ACD), and diopter of spherical power (DS). The study was a part of the Jiangsu Eye Study. The samples were collected from 232 PAC subjects and 306 controls from a population-based prevalence survey conducted in Funing County of Jiangsu, China. The single nucleotide polymorphisms (SNPs) of rs11024102 in PLEKHA7, rs3753841 in COL11A1, and rs1015213 in PCMTD1-ST18 were genotyped by TaqMan-MGB probe using the RT-PCR system. None of the three polymorphisms showed differences in the distribution of genotypes and allele frequencies between the PAC group and the control group. No significant association was determined between the 3 SNPs and AL, ACD, or DS of PAC subjects. We concluded that even though PLEKHA7 rs11024102, COL11A1 rs3753841, and PCMTD1-ST18 rs1015213 are associated with PACG, those sequence variations are not associated with PAC in a Han Chinese population. Our results also did not support a significant role for these three SNPs in ocular biometry such as AL, ACD, and DS.
| S-EPMC3824414 | biostudies-literature
Project description:PurposeTo investigate the different impacts on patient-reported vision-related quality of life (pVRQOL) outcomes in patients with primary angle-closure glaucoma(PACG) and primary open-angle glaucoma(POAG).MethodsProspective cross-sectional study. PACG and POAG patients who had a best-corrected visual acuity(BCVA) in the better eye equal to or better than 20/60, intraocular pressure controlled at or below 25 mmHg and reliable visual field test were invited to participate. The control group included patients with BCVA in the better eye equal to or better than 20/60 and who did not have major eye disease. A validated Taiwanese version of the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25(T)) was performed to assess pVRQOL. The association between each domain of NEI VFQ-25(T) among 3 groups was determined using multivariable linear regression analysis.ResultsA total of 106 PACG, 186 POAG, and 95 controls were enrolled. In multivariable regression analysis of all three groups(PACG/POAG/controls), compared to POAG, PACG showed a weakly positive association with social functioning (R2 = 0.13, ? = 0.22, P = 0.04). PACG showed no significantly negative impact on pVRQOL compared to controls. Taking only glaucoma patients into consideration, PACG patients had a higher score on social functioning compared to POAG (R2 = 0.16, ? = 0.27, P = 0.01). The results of other domains of NEI VFQ-25(T) between the two groups did not differ significantly(p>0.05).ConclusionsIn patients with controlled disease, the impact of PACG and POAG on most domains of NEI VFQ-25(T) were similar, except for better social functioning in PACG compared to POAG.
| S-EPMC5045164 | biostudies-literature
Project description:Current estimates suggest 50% of glaucoma blindness worldwide is caused by primary angle-closure glaucoma (PACG) but the causative gene is not known. We used genetic linkage and whole genome sequencing to identify Spermatogenesis Associated Protein 13, SPATA13 (NM_001166271; NP_001159743, SPATA13 isoform I), also known as ASEF2 (Adenomatous polyposis coli-stimulated guanine nucleotide exchange factor 2), as the causal gene for PACG in a large seven-generation white British family showing variable expression and incomplete penetrance. The 9 bp deletion, c.1432_1440del; p.478_480del was present in all affected individuals with angle-closure disease. We show ubiquitous expression of this transcript in cell lines derived from human tissues and in iris, retina, retinal pigment and ciliary epithelia, cornea and lens. We also identified eight additional mutations in SPATA13 in a cohort of 189 unrelated PACS/PAC/PACG samples. This gene encodes a 1277 residue protein which localises to the nucleus with partial co-localisation with nuclear speckles. In cells undergoing mitosis SPATA13 isoform I becomes part of the kinetochore complex co-localising with two kinetochore markers, polo like kinase 1 (PLK-1) and centrosome-associated protein E (CENP-E). The 9 bp deletion reported in this study increases the RAC1-dependent guanine nucleotide exchange factors (GEF) activity. The increase in GEF activity was also observed in three other variants identified in this study. Taken together, our data suggest that SPATA13 is involved in the regulation of mitosis and the mutations dysregulate GEF activity affecting homeostasis in tissues where it is highly expressed, influencing PACG pathogenesis.
| S-EPMC7233598 | biostudies-literature
Project description:PurposeTo investigate the biometric differences of anterior segment parameters between fellow eyes of acute primary angle closure (F-APAC) and chronic primary angle closure glaucoma (F-CPACG) to get information about differences between APAC and CPAC.MethodsPatients with F-APAC and F-CPACG without prior treatment were enrolled from glaucoma clinics. Parameters were measured on ultrasound biomicroscopy images, including pupil diameter, lens vault (LV), anterior chamber depth, anterior chamber width, iris area, iris thickness (IT 750 and 2000), angle-opening distance (AOD 500 and 750), trabecular-iris space area (TISA 500 and 750), trabecular iris angle (TIA 500 and 750), trabecular-ciliary angle, and ciliary process area. Multivariate logistic regression analysis was performed to determine the most important parameters associated with F-APAC compared with F-CPACG.ResultsFifty-five patients with APAC and 55 patients with CPACG were examined. The anterior chamber depth, IT 750, AOD 750, trabecular iris angle 750, and trabecular-ciliary angle were smaller, and LV and ciliary process area were greater in F-APAC as compared with F-CPACG (P ≤ 0.01). Multivariate logistic regression showed that thinner IT 750, smaller AOD 750, and larger LV were significantly associated with F-APAC (P < 0.01). IT 750 (area under the curve, 0.703) performed relatively better than AOD 750 (area under the curve, 0.696) in distinguishing F-APAC from F-CPACG, with the best cutoff of 0.404 mm and 0.126 mm, respectively.ConclusionsCompared with F-CPACG, F-APAC had thinner peripheral iris, narrower anterior chamber angle, shallower anterior chamber depth, greater LV, larger and anteriorly positioned ciliary body. IT 750, AOD 750, and LV played important roles in distinguishing eyes predisposed to APAC or CPAC.
| S-EPMC8572512 | biostudies-literature
Project description:Purpose:PLEKHA7 and COL11A1 were genotyped for single-nucleotide polymorphisms (SNPs) to investigate the possible association of these two genes with primary angle-closure glaucoma (PACG) and disease severity. Method:A total of 51 PACG cases and 51 normal controls were recruited. Twelve SNPs in the PLEKHA7 (rs216489, rs1027617, rs366590, rs11024060, rs6486330, rs11024097, and rs11024102) and COL11A1 (rs1676484, rs3753841, rs12138977, rs2126642, and rs2622848) genes were genotyped by direct Sanger sequencing. Distributions of allele frequencies and genotype frequencies in cases and controls, as well as in mild, moderate, and severe subgroups, were compared based on mean defect (MD ? 6.00?dB, 6?dB < MD ? 12?dB, and MD > 12?dB were considered mild, moderate, and severe, respectively). Independent Student's t-tests and chi-square tests were used to compare characteristics of PACG cases and controls. Chi-square tests were used to compare the distribution of allele frequencies in cases and controls and in MD-based subgroups with various degrees of glaucoma severity. Binary logistic regression was used to compare the distribution of genotype frequencies and calculate odds ratios (OR) with confidence intervals (CI). Result:Three of the 12 SNPs in COL11A1, rs1676486 (P=0.026, OR = 2.089, 95% CI = 1.092-3.996), rs3753841 (P=0.036, OR = 1.886, 95% CI = 1.038-3.426), and rs12138977 (P=0.024, OR = 2.133, 95% CI = 1.104-4.123) were found to have a significant association with PACG. Furthermore, in the subgroup analysis, rs1676486 (P=0.018, OR = 2.416, 95% CI = 1.284-4.544; P=0.011, OR = 2.119, 95% CI = 1.204-3.729), rs12138977 (P=0.009, OR = 2.158, 95% CI = 1.287-3.618; P=0.006, OR = 1.962, 95% CI = 1.239-3.106), and rs3753841 (P=0.007, OR = 2.550, 95% CI = 1.344-4.839) showed statistically significant differences between moderate/severe groups and controls. Conclusion:Our data suggested that COL11A1 rs1676484, rs3753841, and rs12138977 polymorphisms may be of value for further study as potential gene-dependent risk factors for developing PACG. Moreover, COL11A1 rs1676484 and rs12138977 polymorphisms might be associated with PACG disease severity.
| S-EPMC6369458 | biostudies-literature
Project description:PurposeTo evaluate the association of five different polymorphisms from a genome-wide-associated study with susceptibility to glaucoma in the northeast Iranian population.MethodsHundred and thirty patients with primary angle closure glaucoma (PACG) and 130 healthy controls were genotyped for the polymorphic regions with the aid of tetra-amplification refractory mutation system-polymerase chain reaction. The association of these variants with the disease susceptibility was measured statistically with the logistic regression method.ResultsHundred and thirty patients with PACG (53 males, 77 females) with a mean age of 64.5 ± 6.2 years and 130 healthy control subjects (51 males, 79 females) with a mean age of 64.0 ± 5.7 years were selected for evaluation. There was a significant association between rs3816415 (P = 0.005), rs736893 (P < 0.001), rs7494379 (P < 0.001), and rs1258267 (P = 0.02) with PACG susceptibility. This association could not be shown for rs3739821.ConclusionIt was revealed that studied variants in GLIS3, EPDR1, FERMT2, and CHAT genes can contribute to the incidence of PACG. Additional studies in other populations are needed to evaluate DPM2-FAM102A.
| S-EPMC7001019 | biostudies-literature
Project description:PurposeTo understand the impact of socioeconomic status (SES) on the diagnosis of primary open-angle glaucoma (POAG) and primary angle closure glaucoma (PACG) in Taiwan.MethodsSubjects with glaucoma were identified from the National Health Insurance Research Database of year 2006, which included one million randomly selected insurants. Individuals who had ?4 ambulatory visits within one year which had the diagnosis code of POAG (ICD-9-CM 365.11 or 365.12) or PACG (365.23) and concurrent prescription of anti-glaucoma medication or surgery were selected. Individual SES was represented by monthly income calculated from the insurance premium. Neighborhood SES was defined based on neighborhood household income averages. Urbanization level of habitation was categorized into 3 levels. The odds ratio of having POAG or PACG in subjects with different SES was evaluated by using multiple logistic regression analysis.ResultsIn total, 752 and 561 subjects with POAG and PACG, respectively, who were treated on a regular basis, were identified. The diagnosis of glaucoma was affected by age, gender, frequency of healthcare utilization, individual SES, and urbanization level of habitation. With the adjustment of age, gender, healthcare utilization, neighborhood SES and level of urbanization, subjects with lower income were more likely to be diagnosed as PACG, but less likely as POAG.ConclusionsSubjects with more frequent healthcare utilization were more likely to be diagnosed with glaucoma. Subjects with low SES were more susceptible to PACG, but subjects with high SES were more likely to be diagnosed as POAG. This information is useful for the design and target participant setting in glaucoma education and screening campaign to maximize the efficacy of limited resources in preventing glaucoma blindness.
| S-EPMC4764499 | biostudies-literature