Dataset Information

Lack of Association of rs1192415 in TGFBR3-CDC7 With Visual Field Progression: A Cohort Study in Chinese Open Angle Glaucoma Patients.

ABSTRACT: To investigate the association of known candidate genes with the visual field (VF) progression of primary open angle glaucoma (POAG) in a Han Chinese population. We included 440 POAG patients in this study. Fourteen previously reported single nucleotide polymorphisms (SNPs) at five different gene regions (TGFBR3-CDC7, TMCO1, CDKN2B-AS1, ATOH7, and SIX1/SIX6) were genotyped. Age at diagnosis, gender, intraocular pressure (IOP), mean defect (MD) of VF, vertical cup disk ratio (VCDR), best corrected visual acuity (BCVA), central corneal thickness (CCT), and axial length (AL) were recorded at baseline. Patients were followed up for 5 years to evaluate VF progression over time. Clinical information and allele frequencies of 14 SNPs were compared between patients who progressed and who did not within 5 years by multivariate logistic regression. Survival analysis was performed to evaluate the contribution of the associated SNP by cox regression. Greater MD (P < 0.0001), increased VCDR (P = 0.0001), higher IOP (P = 0.0003), worse BCVA (P = 0.002), and older age (P = 0.030) at the baseline were associated with VF progression. Both multivariate logistic regression and cox regression survival analysis showed none of the 14 SNPs statistically associated with VF progression adjusted with age at diagnosis, gender, baseline MD, follow-up IOP, CCT, and AL. There were lack of association of SNPs at TGFBR3-CDC7, TMCO1, ATOH7, CDKN2B-AS1, SIX1/SIX6 loci with VF progression in POAG patients in Han Chinese. Further studies are needed to evaluate the association of genetic variants with VF progression.

SUBMITTER: Chen Y

PROVIDER: S-EPMC6208000 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Lack of Association of rs1192415 in TGFBR3-CDC7 With Visual Field Progression: A Cohort Study in Chinese Open Angle Glaucoma Patients.

Chen Yuhong Y Qiu Chen C Qian Shaohong S Chen Junyi J Chen Xueli X Wang Li L Sun Xinghuai X

Frontiers in genetics 20181024

To investigate the association of known candidate genes with the visual field (VF) progression of primary open angle glaucoma (POAG) in a Han Chinese population. We included 440 POAG patients in this study. Fourteen previously reported single nucleotide polymorphisms (SNPs) at five different gene regions (TGFBR3-CDC7, TMCO1, CDKN2B-AS1, ATOH7, and SIX1/SIX6) were genotyped. Age at diagnosis, gender, intraocular pressure (IOP), mean defect (MD) of VF, vertical c ...[more]

PMID: 30405695

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Project description:PurposeThe influence of myopia on glaucoma progression remains unknown, possibly because of the multifactorial nature of glaucoma and difficulty in assessing a solo contribution of myopia. The purpose of this study is to investigate the association of myopia with visual field (VF) progression in glaucoma using a paired-eye design to minimize the influence of confounding systemic factors that are diverse among individuals.MethodsThis retrospective study evaluated 144 eyes of 72 subjects with open-angle glaucoma, with similar intra-ocular pressure between paired eyes, spherical equivalent (SE) ≤ -2 diopter (D), and axial length ≥ 24 mm. Paired eyes with faster and slower VF progression were grouped separately, according to the global VF progression rate assessed by automated pointwise linear regression analysis. The SE, axial length, tilt ratio and torsion angle of optic discs, Bruch's membrane (BM) opening area, and gamma zone parapapillary atrophy (PPA) width were compared between the two groups. Factors associated with faster VF progression were determined by logistic regression analysis.ResultsThe mean follow-up duration was 8.9 ± 4.4 years. The mean value of SE and axial length were -6.31 ± 1.88 D and 26.05 ± 1.12 mm, respectively. The mean global visual field progression rate was -0.32 ± 0.38 dB/y. Tilt ratio, BM opening area, and gamma zone PPA width were significantly greater in the eyes with faster VF progression than those with slower progression. In multivariate analysis, these factors were significantly associated with faster VF progression (all P < 0.05), while SE and axial length were not associated with it.ConclusionIn myopic glaucoma subjects, tilt of the optic disc and temporal shifting and enlargement of the BM opening were associated with faster rate of VF progression between paired eyes. This suggests that myopia influences VF progression in glaucomatous eyes via optic disc deformations rather than via refractive error itself.

Project description:BACKGROUND:Primary angle-closure glaucoma is a type of glaucoma associated with a physically obstructed anterior chamber angle. Obstruction of the anterior chamber angle blocks drainage of fluids (aqueous humor) within the eye and may raise intraocular pressure (IOP). Elevated IOP is associated with glaucomatous optic nerve damage and visual field loss. Laser peripheral iridotomy (often just called 'iridotomy') is a procedure to eliminate pupillary block by allowing aqueous humor to pass directly from the posterior to anterior chamber through use of a laser to create a hole in the iris. It is commonly used to treat patients with primary angle-closure glaucoma, patients with primary angle closure (narrow angles and no signs of glaucomatous optic neuropathy), and patients who are primary angle-closure suspects (patients with reversible obstruction). The effectiveness of iridotomy on slowing progression of visual field loss, however, is uncertain. OBJECTIVES:To assess the effects of iridotomy compared with no iridotomy for primary angle-closure glaucoma, primary angle closure, and primary angle-closure suspects. SEARCH METHODS:We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 9) which contains the Cochrane Eyes and Vision Trials Register; MEDLINE Ovid; Embase Ovid; PubMed; LILACS; ClinicalTrials.gov; and the ICTRP. The date of the search was 18 October 2017. SELECTION CRITERIA:Randomized or quasi-randomized controlled trials that compared iridotomy to no iridotomy in primary angle-closure suspects, patients with primary angle closure, or patients with primary angle-closure glaucoma in one or both eyes were eligible. DATA COLLECTION AND ANALYSIS:Two authors worked independently to extract data on study characteristics, outcomes for the review, and risk of bias in the included studies. We resolved differences through discussion. MAIN RESULTS:We identified two trials (2502 eyes of 1251 participants) that compared iridotomy to no iridotomy. Both trials recruited primary angle suspects from Asia and randomized one eye of each participant to iridotomy and the other to no iridotomy. Because the full trial reports are not yet available for both trials, no data are available to assess the effectiveness of iridotomy on slowing progression of visual field loss, change in IOP, need for additional surgeries, number of medications needed to control IOP, mean change in best-corrected visual acuity, and quality of life. Based on currently reported data, one trial showed evidence that iridotomy increases angle width at 18 months (by 12.70°, 95% confidence interval (CI) 12.06° to 13.34°, involving 1550 eyes, moderate-certainty evidence) and may be associated with IOP spikes at one hour after treatment (risk ratio 24.00 (95% CI 7.60 to 75.83), involving 1468 eyes, low-certainty evidence). The risk of bias of the two studies was overall unclear due to lack of availability of a full trial report. AUTHORS' CONCLUSIONS:The available studies that directly compared iridotomy to no iridotomy have not yet published full trial reports. At present, we cannot draw reliable conclusions based on randomized controlled trials as to whether iridotomy slows progression of visual field loss at one year compared to no iridotomy. Full publication of the results from the studies may clarify the benefits of iridotomy.

Project description:Background: Primary open-angle glaucoma (POAG) patients exhibit widespread white matter (WM) degeneration throughout their visual pathways. Whether this degeneration starts at the pre- or post-geniculate pathways remains unclear. In this longitudinal study, we assess the progression of WM degeneration exhibited by the pre-geniculate optic tracts (OTs) and the post-geniculate optic radiations (ORs) of POAG patients over time, aiming to determine the source and pattern of spread of this degeneration. Methods: Diffusion-weighted MRI scans were acquired for 12 POAG patients and 14 controls at two time-points 5.4 ± 2.1 years apart. Fiber density (FD), an estimate of WM axonal density, was computed for the OTs and ORs of all participants in an unbiased longitudinal population template space. First, FD was compared between POAG patients and the controls at time-point 1 (TP1) and time-point 2 (TP2) independently. Secondly, repeated measures analysis was performed for FD change in POAG patients between the two time-points. Finally, we compared the rate of FD change over time between the two groups. Results: Compared to the controls, POAG patients exhibited significantly lower FD in the left OT at TP1 and in both OTs and the left OR at TP2. POAG patients showed a significant loss of FD between the time-points in the right OT and both ORs, while the left OR showed a significantly higher rate of FD loss in POAG patients compared to the controls. Conclusions: We find longitudinal progression of neurodegenerative WM changes in both the pre- and post-geniculate visual pathways of POAG patients. The pattern of changes suggests that glaucomatous WM degeneration starts at the pre-geniculate pathways and then spreads to the post-geniculate pathways. Furthermore, we find evidence that the trans-synaptic spread of glaucomatous degeneration to the post-geniculate pathways is a prolonged process which continues in the absence of detectable pre-geniculate degenerative progression. This suggests the presence of a time window for salvaging intact post-geniculate pathways, which could prove to be a viable therapeutic target in the future.

Dataset Information

Lack of Association of rs1192415 in TGFBR3-CDC7 With Visual Field Progression: A Cohort Study in Chinese Open Angle Glaucoma Patients.

Publications

Lack of Association of rs1192415 in <i>TGFBR3-CDC7</i> With Visual Field Progression: A Cohort Study in Chinese Open Angle Glaucoma Patients.

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