A common variant near TGFBR3 is associated with primary open angle glaucoma

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited.Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease with a significant genetic contribution.We performed Exome Array (Illumina) analysis on 3504 POAG cases and 9746 controls with replication of the most significant findings in 9173 POAG cases and 26 780 controls across 18 collections of Asian, African and European descent. Apart from confirming strong evidence of association at CDKN2B-AS1 (rs2157719 [G], odds ratio [OR] = 0.71, P = 2.81 × 10−33), we observed one SNP showing significant association to POAG (CDC7–TGFBR3 rs1192415, ORG-allele = 1.13, Pmeta = 1.60 × 10−8). This particular SNP has previously been shown to be strongly associated with optic disc area and vertical cup-to-disc ratio, which are regarded as glaucoma-related quantitative traits. Our study now extends this by directly implicating it in POAG disease pathogenesis

A common variant near TGFBR3 is associated with primary open angle glaucoma

Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease with a significant genetic contribution. We performed Exome Array (Illumina) analysis on 3504 POAG cases and 9746 controls with replication of the most significant findings in 9173 POAG cases and 26 780 controls across 18 collections of Asian, African and European descent. Apart from confirming strong evidence of association at CDKN2B-AS1 (rs2157719 [G], odds ratio [OR] = 0.71, P = 2.81 × 10−33), we observed one SNP showing significant association to POAG (CDC7–TGFBR3 rs1192415, ORG-allele = 1.13, Pmeta = 1.60 × 10−8). This particular SNP has previously been shown to be strongly associated with optic disc area and vertical cup-to-disc ratio, which are regarded as glaucoma-related quantitative traits. Our study now extends this by directly implicating it in POAG disease pathogenesis

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Abstract Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease with a significant genetic contribution. We performed Exome Array ), we observed one SNP showing significant association to POAG (CDC7-TGFBR3 rs1192415, OR G-allele = 1.13, P meta = 1.60 × 10 −8 ). This particular SNP has previously been shown to be strongly associated with optic disc area and vertical cup-to-disc ratio, which are regarded as glaucoma-related quantitative traits. Our study now extends this by directly implicating it in POAG disease pathogenesis

Outcomes of rhegmatogenous retinal detachment surgery in eyes with pre-existing glaucoma drainage devices

Purpose: To evaluate the outcome of rhegmatogenous retinal detachment (RRD) surgery in eyes with preplaced glaucoma drainage device (GDD) with respect to intraocular pressure (IOP) control as well as success of retinal detachment (RD) surgery. Methods: It is a retrospective case series. The case records of patients who underwent RD surgery after GDD implantation from 2000 to 2014 were screened. The demographic data, ocular examination findings at all visits, details pertaining to retinal detachment and its repair, and the postoperative course was documented. Results: Twelve patients were included in study. The mean age of patients was 24.3 years (median 11 years; range 3-72 years). Male: Female ratio was 3:1. Mean duration between GDD and RD was 24 months (4 days-91 months). Of the ten eyes that underwent surgery, nine eyes underwent pars plana vitrectomy, and in one eye scleral buckling was done. GDD was removed only in one eye. At final follow-up, retina was attached with controlled IOP in 6 (60%) eyes, of which 5 (50%) had improvement in best corrected visual acuity. Conclusion: Pars plana vitrectomy was required in almost all cases for the management of RD in eyes with preplaced GDD. Retinal reattachment with good IOP control could be achieved in 60% of eyes. Removal of the drainage device was not essential for the effective management of the RRD in most cases. With multidisciplinary approach, close follow-up and timely intervention, vision can be preserved along with glaucoma control and successful retinal reattachment

Clinical utility, feasibility of home tonometry using iCare HOME by glaucoma patients

Purpose: To determine agreement between diurnal variation testing (DVT) of intraocular pressure (IOP) with Goldmann applanation tonometer (GAT) and iCare HOME (IH) by an optometrist (OP) and home monitoring by participants (PT). Methods: Patients (18–80 years) with glaucoma and suspects were enrolled. IH IOP and GAT were taken by an OP at 2 h intervals from 8 AM to 4 PM on Day 1 and PT between 6 AM and 9 PM, for the next 2 days. IOP, date, and time were viewed via iCare LINK software. Results: In total, 72.9% (51/70) PT trained were able to take reliable readings. One hundred two eyes (51 patients, age 53 ± 16 yrs) were analyzed. Correlation between optometrist (OP) and participants (PT) was strong and positive {IH OP-IH PT- r = 0.90, p-0.0001;IH PT-GAT- r = 0.79, p-0.0001}. Agreement by Bland Altman plots was limited {IH OP-IH PT mean 0.1 mmHg (95% LOA -5.3 to 5.5), IH PT-GAT 2.2 mmHg (-5.7 to 10.1)}. Intraclass correlation coefficient for IH OP-IH PT was 1.18 (95% CI 1.37-1.09). Intradevice {0.95 (95% CI 0.94-0.97)} and interrater repeatability {0.91 (0.79–0.96)} were good. 37% of eyes had a synchronous peak on GAT and IH during the day DVT. Conclusion: Home tonometry by iCare HOME is easy, feasible, but due to limited agreement cannot substitute GAT DVT

Genome-wide association analyses identify three new susceptibility loci for primary angle closure glaucoma.

Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study including 1,854 PACG cases and 9,608 controls across 5 sample collections in Asia. Replication experiments were conducted in 1,917 PACG cases and 8,943 controls collected from a further 6 sample collections. We report significant associations at three new loci: rs11024102 in PLEKHA7 (per-allele odds ratio (OR)=1.22; P=5.33×10(-12)), rs3753841 in COL11A1 (per-allele OR=1.20; P=9.22×10(-10)) and rs1015213 located between PCMTD1 and ST18 on chromosome 8q (per-allele OR=1.50; P=3.29×10(-9)). Our findings, accumulated across these independent worldwide collections, suggest possible mechanisms explaining the pathogenesis of PACG

ABCC5, a Gene That Influences the Anterior Chamber Depth, Is Associated with Primary Angle Closure Glaucoma.

Anterior chamber depth (ACD) is a key anatomical risk factor for primary angle closure glaucoma (PACG). We conducted a genome-wide association study (GWAS) on ACD to discover novel genes for PACG on a total of 5,308 population-based individuals of Asian descent. Genome-wide significant association was observed at a sequence variant within ABCC5 (rs1401999; per-allele effect size = -0.045 mm, P = 8.17×10-9). This locus was associated with an increase in risk of PACG in a separate case-control study of 4,276 PACG cases and 18,801 controls (per-allele OR = 1.13 [95% CI: 1.06-1.22], P = 0.00046). The association was strengthened when a sub-group of controls with open angles were included in the analysis (per-allele OR = 1.30, P = 7.45×10-9; 3,458 cases vs. 3,831 controls). Our findings suggest that the increase in PACG risk could in part be mediated by genetic sequence variants influencing anterior chamber dimensions. PLoS Genet 2014 Mar 6; 10(3):e1004089

Genome-wide association study identifies five new susceptibility loci for primary angle closure glaucoma.

Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study (GWAS) followed by replication in a combined total of 10,503 PACG cases and 29,567 controls drawn from 24 countries across Asia, Australia, Europe, North America, and South America. We observed significant evidence of disease association at five new genetic loci upon meta-analysis of all patient collections. These loci are at EPDR1 rs3816415 (odds ratio (OR) = 1.24, P = 5.94 × 10(-15)), CHAT rs1258267 (OR = 1.22, P = 2.85 × 10(-16)), GLIS3 rs736893 (OR = 1.18, P = 1.43 × 10(-14)), FERMT2 rs7494379 (OR = 1.14, P = 3.43 × 10(-11)), and DPM2-FAM102A rs3739821 (OR = 1.15, P = 8.32 × 10(-12)). We also confirmed significant association at three previously described loci (P < 5 × 10(-8) for each sentinel SNP at PLEKHA7, COL11A1, and PCMTD1-ST18), providing new insights into the biology of PACG

Genome-wide association study identifies five new susceptibility loci for primary angle closure glaucoma.

Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study (GWAS) followed by replication in a combined total of 10,503 PACG cases and 29,567 controls drawn from 24 countries across Asia, Australia, Europe, North America, and South America. We observed significant evidence of disease association at five new genetic loci upon meta-analysis of all patient collections. These loci are at EPDR1 rs3816415 (odds ratio (OR) = 1.24, P = 5.94 × 10(-15)), CHAT rs1258267 (OR = 1.22, P = 2.85 × 10(-16)), GLIS3 rs736893 (OR = 1.18, P = 1.43 × 10(-14)), FERMT2 rs7494379 (OR = 1.14, P = 3.43 × 10(-11)), and DPM2-FAM102A rs3739821 (OR = 1.15, P = 8.32 × 10(-12)). We also confirmed significant association at three previously described loci (P < 5 × 10(-8) for each sentinel SNP at PLEKHA7, COL11A1, and PCMTD1-ST18), providing new insights into the biology of PACG