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Factors associated with achieving intraocular pressure lower than 15 mmHg by Trabectome surgery in primary open-angle glaucoma.

ABSTRACT: To assess good prognostic factors of Trabectome surgery in primary open-angle glaucoma (POAG), clinical records of patients with POAG who underwent Trabectome surgery with/without cataract surgery as the first additive therapy to eye drops between January 2015 and March 2018 were retrospectively reviewed. Overall, data of 79 eyes (79 patients; 50 men; mean age, 68.0 years) up to postoperative 24 months were analyzed. Their mean intraocular pressure (IOP) was 20.4 ± 6.0 mmHg at baseline. Forty-two eyes (53.2%) achieved an IOP < 15 mmHg and ≥ 20% reduction from baseline without additional treatments. Phakic eyes had a better survival probability than pseudophakic eyes after adjusting for age, sex, baseline IOP, best-corrected visual acuity, and eye drop score (hazard ratio 3.096; 95% confidence interval [95% CI] 1.367-7.013; P = 0.007). Phakic eyes treated with combined Trabectome and cataract surgeries (mean survival time, 22.250 months; 95% CI 17.606-26.894) had a better survival probability than pseudophakic eyes treated with Trabectome surgery only (mean survival time, 12.111 months; 95% CI 8.716-15.506; P = 0.009) after the adjustment. Among the eyes treated with Trabectome surgery only, phakic eyes required significantly less additional treatments than pseudophakic eyes (P = 0.04). Trabectome surgery may be indicated for phakic eyes with POAG in addition to eye-drop therapy.

SUBMITTER: Nakamura K

PROVIDER: S-EPMC8275622 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Common genetic determinants of intraocular pressure and primary open-angle glaucoma.

Project description:Intraocular pressure (IOP) is a highly heritable risk factor for primary open-angle glaucoma and is the only target for current glaucoma therapy. The genetic factors which determine IOP are largely unknown. We performed a genome-wide association study for IOP in 11,972 participants from 4 independent population-based studies in The Netherlands. We replicated our findings in 7,482 participants from 4 additional cohorts from the UK, Australia, Canada, and the Wellcome Trust Case-Control Consortium 2/Blue Mountains Eye Study. IOP was significantly associated with rs11656696, located in GAS7 at 17p13.1 (p=1.4×10(-8)), and with rs7555523, located in TMCO1 at 1q24.1 (p=1.6×10(-8)). In a meta-analysis of 4 case-control studies (total N?=?1,432 glaucoma cases), both variants also showed evidence for association with glaucoma (p=2.4×10(-2) for rs11656696 and p=9.1×10(-4) for rs7555523). GAS7 and TMCO1 are highly expressed in the ciliary body and trabecular meshwork as well as in the lamina cribrosa, optic nerve, and retina. Both genes functionally interact with known glaucoma disease genes. These data suggest that we have identified two clinically relevant genes involved in IOP regulation.

| S-EPMC3342933 | biostudies-literature

Genetic correlations between intraocular pressure, blood pressure and primary open-angle glaucoma: a multi-cohort analysis.

Project description:Primary open-angle glaucoma (POAG) is the most common chronic optic neuropathy worldwide. Epidemiological studies show a robust positive relation between intraocular pressure (IOP) and POAG and modest positive association between IOP and blood pressure (BP), while the relation between BP and POAG is controversial. The International Glaucoma Genetics Consortium (n=27 558), the International Consortium on Blood Pressure (n=69 395), and the National Eye Institute Glaucoma Human Genetics Collaboration Heritable Overall Operational Database (n=37 333), represent genome-wide data sets for IOP, BP traits and POAG, respectively. We formed genome-wide significant variant panels for IOP and diastolic BP and found a strong relation with POAG (odds ratio and 95% confidence interval: 1.18 (1.14-1.21), P=1.8 × 10-27) for the former trait but no association for the latter (P=0.93). Next, we used linkage disequilibrium (LD) score regression, to provide genome-wide estimates of correlation between traits without the need for additional phenotyping. We also compared our genome-wide estimate of heritability between IOP and BP to an estimate based solely on direct measures of these traits in the Erasmus Rucphen Family (ERF; n=2519) study using Sequential Oligogenic Linkage Analysis Routines (SOLAR). LD score regression revealed high genetic correlation between IOP and POAG (48.5%, P=2.1 × 10-5); however, genetic correlation between IOP and diastolic BP (P=0.86) and between diastolic BP and POAG (P=0.42) were negligible. Using SOLAR in the ERF study, we confirmed the minimal heritability between IOP and diastolic BP (P=0.63). Overall, IOP shares genetic basis with POAG, whereas BP has limited shared genetic correlation with IOP or POAG.

| S-EPMC5643970 | biostudies-literature

Additive effects of genetic variants associated with intraocular pressure in primary open-angle glaucoma.

Project description:To investigate the association between the additive effects of genetic variants associated with intraocular pressure (IOP) and IOP, vertical cup-to-disc ratio (VCDR), and high tension glaucoma (HTG) or normal tension glaucoma (NTG) as phenotypic features of primary open-angle glaucoma (POAG), and to evaluate the clinical usefulness of the additive effects of IOP-related genetic variants for predicting IOP elevation, Japanese patients with HTG (n = 255) and NTG (n = 261) and 246 control subjects were genotyped for nine IOP-related genetic variants near CAV2, GAS7, GLCCI1/ICA1, ABCA1, ARHGEF12, FAM125B, FNDC3B, ABO, and PTPRJ/AGBL2. The total number of risk alleles of these genetic variants was calculated for each participant as a genetic risk score (GRS), and the association between the GRS and the maximum IOP, mean VCDR, and phenotype (HTG or NTG) of POAG was evaluated. As the GRS increased, the maximum IOP (P = 0.012) and VCDR (P = 0.010) significantly increased. The GRS (9.1±1.9) in patients with HTG was significantly higher (P = 0.011) than that (8.7±1.8) in control subjects. The patients with GRS?12 as a cut-off value had a 2.54 times higher (P = 0.0085) risk on HTG (maximum IOP?22mmHg) compared with all patients. The IOP-related GRS approach substantiated that the IOP and VCDR were increased by the additive effects of IOP-related genetic variants in POAG. The high IOP-related GRS in patients with HTG but not NTG shows that there are differences in the genetic background between HTG and NTG and supports the notion that the phenotype (HTG or NTG) in patients with POAG depends on the additive effects of IOP-related genetic variants. The above-mentioned cut-off value of IOP-related GRS may be clinically useful for predicting the risk of IOP elevation.

| S-EPMC5568337 | biostudies-literature

Comparison of self-measured diurnal intraocular pressure profiles using rebound tonometry between primary angle closure glaucoma and primary open angle glaucoma patients.

Project description:PurposeTo document the diurnal intraocular pressure (IOP) profile with rebound tonometry performed by primary glaucoma patients in non-clinic environment.Patients and methodsFifty-three medically-treated eyes of 31 primary angle closure glaucoma (PACG) and 22 primary open angle glaucoma (POAG) patients with no previous eye surgery were recruited. Diurnal IOP was measured 5 times per day at four-hourly intervals from 08:00 to 24:00 for 1 week in patients' study eye using rebound tonometry in a non-clinic environment. The diurnal IOP profiles were compared between PACG and POAG eyes.ResultsFor both PACG and POAG eyes, mean patient-measured IOP was highest in the morning, gradually decreased over the course of a day, and was lowest by midnight (p < 0.001). The diurnal IOP fluctuation ± 1 standard deviation (SD), as documented by SD in daily IOP values, was lower in PACG group (1.6 ± 1.1 mmHg) than in POAG group (2.0 ± 1.2 mmHg; p = 0.049). The mean trough IOP ± 1 SD was higher in PACG group (12.9 ± 2.8 mmHg), compared to POAG group (11.5 ± 3.8 mmHg; p = 0.041). The mean IOP level at midnight ± 1 SD in PACG group (14.0 ± 3.2 mmHg) was higher than that in POAG group (12.1 ± 3.7 mmHg; p = 0.013).ConclusionsIOP in primary glaucoma patients was highest in the morning, and decreased over the course of a day in non-clinic environment. Treated diurnal IOP fluctuation seemed to be greater in POAG than PACG eyes.

| S-EPMC5363915 | biostudies-literature

Adjusting intraocular pressure for central corneal thickness does not improve prediction models for primary open-angle glaucoma.

Project description:PurposeTo determine if the accuracy of the baseline prediction model for the development of primary open-angle glaucoma (POAG) in patients with ocular hypertension can be improved by correcting intraocular pressure (IOP) for central corneal thickness (CCT).DesignReanalysis of the baseline prediction model for the development of POAG from the Ocular Hypertension Treatment Study (OHTS) substituting IOP adjusted for CCT using 5 different correction formulae for unadjusted IOP.ParticipantsA total of 1433 of 1636 participants randomized to OHTS who had complete baseline data for factors in the prediction model: age, IOP, CCT, vertical cup-to-disc ratio (VCDR), and pattern standard deviation (PSD).MethodsReanalysis of the prediction model for the risk of developing POAG using the same baseline variables (age, IOP, CCT, VCDR, and PSD) except that IOP was adjusted for CCT using correction formulae. A separate Cox proportional hazards model was run using IOP adjusted for CCT by each of the 5 formulae published to date. Models were run including and excluding CCT.Main outcome measuresPredictive accuracy of each Cox proportional hazards model was assessed using the c-statistic and calibration chi-square.ResultsC-statistics for prediction models that used IOP adjusted for CCT by various formulas ranged from 0.75 to 0.77, no better than the original prediction model (0.77) that did not adjust IOP for CCT. Calibration chi-square was acceptable for all models. Baseline IOP, whether adjusted for CCT or not, was statistically significant in all models including those with CCT in the same model. The CCT was statistically significant in all models including those with IOP adjusted for CCT in the same model.ConclusionsThe calculation of individual risk for developing POAG in ocular hypertensive individuals is simpler and equally accurate using IOP and CCT as measured, rather than applying an adjustment formula to correct IOP for CCT.

| S-EPMC3184359 | biostudies-literature

Variation in Intraocular Pressure and the Risk of Developing Open-Angle Glaucoma: The Los Angeles Latino Eye Study.

Project description:PURPOSE:To determine whether measures of intraocular pressure (IOP) variation are independently associated with the risk of developing open-angle glaucoma (OAG). DESIGN:A population-based, longitudinal study. METHODS:A total of 3666 Latinos free of OAG at the baseline of the Los Angeles Latino Eye Study were followed up 4 years later. Maximum IOP, standard deviation (SD) of IOP, range of IOP, and mean IOP were derived from 6 readings obtained at the 2 visits. OAG diagnosis at each visit was based on the consensus of experts who had access to all clinical examination data from that visit. Multivariate logistic regression was performed. RESULTS:Maximum, SD, and range of IOP were all associated with risk of developing OAG, and SD and range of IOP remained significantly associated even after adjustment for mean IOP. Maximum IOP provided the best fit to the data and other IOP measures were not associated with OAG risk in the model that had included maximum IOP. The effect of IOP variation varied by the level of IOP. Among participants with higher IOPs (?15 mm Hg), only higher levels of maximum IOP were associated with a higher OAG risk (P < .05), while SD and range of IOP were not associated with OAG risk. Among participants with lower IOPs (<15 mm Hg), higher levels of maximum, SD, and range of IOP were all associated with a higher risk of developing OAG (P < .05). Mean IOP was associated with OAG risk only in participants with higher IOPs and not in those with lower IOPs. Results were similar when participants were stratified as <18 and ?18 mm Hg. CONCLUSIONS:IOP variation was an independent risk factor for OAG. Maximum IOP was the most consistent IOP measure for predicting OAG risk across the entire spectrum of IOPs, possibly by capturing the effect of IOP variation among persons with relative lower IOPs as well as mean IOP effects in those with higher IOPs.

| S-EPMC5871564 | biostudies-literature

Magnetic Resonance Imaging of Optic Nerve Traction During Adduction in Primary Open-Angle Glaucoma With Normal Intraocular Pressure.

Project description:We used magnetic resonance imaging (MRI) to ascertain effects of optic nerve (ON) traction in adduction, a phenomenon proposed as neuropathic in primary open-angle glaucoma (POAG).Seventeen patients with POAG and maximal IOP ≤ 20 mm Hg, and 31 controls underwent MRI in central gaze and 20° to 30° abduction and adduction. Optic nerve and sheath area centroids permitted computation of midorbital lengths versus minimum paths.Average mean deviation (±SEM) was -8.2 ± 1.2 dB in the 15 patients with POAG having interpretable perimetry. In central gaze, ON path length in POAG was significantly more redundant (104.5 ± 0.4% of geometric minimum) than in controls (102.9 ± 0.4%, P = 2.96 × 10-4). In both groups the ON became significantly straighter in adduction (28.6 ± 0.8° in POAG, 26.8 ± 1.1° in controls) than central gaze and abduction. In adduction, the ON in POAG straightened to 102.0% ± 0.2% of minimum path length versus 104.5% ± 0.4% in central gaze (P = 5.7 × 10-7), compared with controls who straightened to 101.6% ± 0.1% from 102.9% ± 0.3% in central gaze (P = 8.7 × 10-6); and globes retracted 0.73 ± 0.09 mm in POAG, but only 0.07 ± 0.08 mm in controls (P = 8.8 × 10-7). Both effects were confirmed in age-matched controls, and remained significant after correction for significant effects of age and axial globe length (P = 0.005).Although tethering and elongation of ON and sheath are normal in adduction, adduction is associated with abnormally great globe retraction in POAG without elevated IOP. Traction in adduction may cause mechanical overloading of the ON head and peripapillary sclera, thus contributing to or resulting from the optic neuropathy of glaucoma independent of IOP.

| S-EPMC5566384 | biostudies-other

Plasma GDF-15 concentration is not elevated in open-angle glaucoma.

Project description:AimRecently, the level of growth differentiation factor 15 (GDF-15) in blood, was proposed as biomarker to detect mitochondrial dysfunction. In the current study, we evaluate this biomarker in open-angle glaucoma (OAG), as there is increasing evidence that mitochondrial dysfunction plays a role in the pathophysiology of this disease.MethodsPlasma GDF-15 concentrations were measured with ELISA in 200 OAG patients and 61 age-matched controls (cataract without glaucoma). The OAG patient group consisted of high tension glaucoma (HTG; n = 162) and normal tension glaucoma (NTG; n = 38). Groups were compared using the Kruskal-Wallis nonparametric test with Dunn's multiple comparison post-hoc correction. GDF-15 concentration was corrected for confounders identified with forward linear regression models.ResultsBefore correcting for confounders, median plasma GDF-15 levels was significantly lower in the combined OAG group (p = 0.04), but not when analysing HTG and NTG patients separately. Forward linear regression analysis showed that age, gender, smoking and systemic hypertension were significant confounders affecting GDF-15 levels. After correction for these confounders, GDF-15 levels in OAG patients were no longer significantly different from controls. Subgroup analysis of the glaucoma patients did not show a correlation between disease severity and plasma GDF-15, but did reveal that for NTG patients, intake of dietary supplements, which potentially improve mitochondrial function, correlated with lower plasma GDF-15.ConclusionThe present study suggests that plasma GDF-15 is not suited as biomarker of mitochondrial dysfunction in OAG patients.

| S-EPMC8162581 | biostudies-literature

Genome-wide analyses identify 68 new loci associated with intraocular pressure and improve risk prediction for primary open-angle glaucoma.

Project description:Glaucoma is the leading cause of irreversible blindness globally 1 . Despite its gravity, the disease is frequently undiagnosed in the community 2 . Raised intraocular pressure (IOP) is the most important risk factor for primary open-angle glaucoma (POAG)3,4. Here we present a meta-analysis of 139,555 European participants, which identified 112 genomic loci associated with IOP, 68 of which are novel. These loci suggest a strong role for angiopoietin-receptor tyrosine kinase signaling, lipid metabolism, mitochondrial function and developmental processes underlying risk for elevated IOP. In addition, 48 of these loci were nominally associated with glaucoma in an independent cohort, 14 of which were significant at a Bonferroni-corrected threshold. Regression-based glaucoma-prediction models had an area under the receiver operating characteristic curve (AUROC) of 0.76 in US NEIGHBORHOOD study participants and 0.74 in independent glaucoma cases from the UK Biobank. Genetic-prediction models for POAG offer an opportunity to target screening and timely therapy to individuals most at risk.

| S-EPMC5985943 | biostudies-literature

New insights into the genetics of primary open-angle glaucoma based on meta-analyses of intraocular pressure and optic disc characteristics.

Project description:Primary open-angle glaucoma (POAG), the most common optic neuropathy, is a heritable disease. Siblings of POAG cases have a ten-fold increased risk of developing the disease. Intraocular pressure (IOP) and optic nerve head characteristics are used clinically to predict POAG risk. We conducted a genome-wide association meta-analysis of IOP and optic disc parameters and validated our findings in multiple sets of POAG cases and controls. Using imputation to the 1000 genomes (1000G) reference set, we identified 9 new genomic regions associated with vertical cup-disc ratio (VCDR) and 1 new region associated with IOP. Additionally, we found 5 novel loci for optic nerve cup area and 6 for disc area. Previously it was assumed that genetic variation influenced POAG either through IOP or via changes to the optic nerve head; here we present evidence that some genomic regions affect both IOP and the disc parameters. We characterized the effect of the novel loci through pathway analysis and found that pathways involved are not entirely distinct as assumed so far. Further, we identified a novel association between CDKN1A and POAG. Using a zebrafish model we show that six6b (associated with POAG and optic nerve head variation) alters the expression of cdkn1a. In summary, we have identified several novel genes influencing the major clinical risk predictors of POAG and showed that genetic variation in CDKN1A is important in POAG risk.

| S-EPMC5968632 | biostudies-literature

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