Dataset Information

Progression of Primary Open-Angle Glaucoma in Diabetic and Nondiabetic Patients.

ABSTRACT: PURPOSE:To compare the rates of visual field (VF) loss and retinal nerve fiber layer (RNFL) thinning in primary open-angle glaucoma (POAG) patients with or without type 2 diabetes mellitus (DM). DESIGN:Cohort study. METHODS:A total of 197 eyes (55 eyes of 32 POAG patients with DM in POAG/DM group and 142 eyes of 111 age-matched POAG patients without DM in POAG/DM- group) were included from the Diagnostic Innovations in Glaucoma Study (DIGS). Type 2 DM participants were defined by self-report of DM history and use of antidiabetic medication. The rates of VF loss and RNFL loss were compared in POAG eyes with and without DM using univariate and multivariable mixed-effects models. RESULTS:The median (interquartile range) follow-up was 5.7 years (4.0, 6.4). The mean rate of global RNFL loss in the POAG/DM group was 2-fold slower than in the POAG/DM- group overall (-0.40 ?m/year vs -0.83 ?m/year, respectively P = .01). Although a slower rate of VF mean deviation and pattern standard deviation loss was found in the POAG/DM group compared to the POAG/DM- group, the difference was not statistically significant. CONCLUSIONS:POAG patients with treated type 2 DM, who had no detectable diabetic retinopathy, had significantly slower rates of RNFL thinning compared to those without diagnosed DM.

SUBMITTER: Hou H

PROVIDER: S-EPMC5916320 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Progression of Primary Open-Angle Glaucoma in Diabetic and Nondiabetic Patients.

Hou Huiyuan H Shoji Takuhei T Zangwill Linda M LM Moghimi Sasan S Saunders Luke J LJ Hasenstab Kyle K Ghahari Elham E Manalastas Patricia Isabel C PIC Akagi Tadamichi T Christopher Mark M Penteado Rafaella C RC Weinreb Robert N RN

American journal of ophthalmology 20180213

<h4>Purpose</h4>To compare the rates of visual field (VF) loss and retinal nerve fiber layer (RNFL) thinning in primary open-angle glaucoma (POAG) patients with or without type 2 diabetes mellitus (DM).<h4>Design</h4>Cohort study.<h4>Methods</h4>A total of 197 eyes (55 eyes of 32 POAG patients with DM in POAG/DM group and 142 eyes of 111 age-matched POAG patients without DM in POAG/DM- group) were included from the Diagnostic Innovations in Glaucoma Study (DIGS). Type 2 DM participants were defi ...[more]

PMID: 29447914

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Project description:PURPOSE: Glaucoma is a heterogeneous group of optic neuropathies with a complex genetic basis. To date, only the following four genes have been identified: viz. myocilin (MYOC), optineurin (OPTN), WD repeat domain 36 (WDR36), and neurotrophin 4 (NTF4). However, there are conflicting reports regarding the involvement of WDR36 in the pathogenesis of primary open-angle glaucoma (POAG). In the Asian population, mutations in WDR36 appear to play a minor role in POAG pathogenesis but polymorphic variants have been found to be associated with POAG, especially in patients with high tension glaucoma (HTG). The purpose of this study is to determine the role of WDR36 in East Indian POAG patients. To date, no other studies have yet examined this role. METHODS: Ten single nucleotide polymorphisms (SNPs; rs1971050, rs1993465, rs13153937, rs10038177, rs11241095, rs10043631, rs10038058, rs10491424, rs17553936, and rs13186912) spanning almost the entire WDR36 gene were selected and their association with eastern Indian POAG patients was evaluated. Our study pool consisted of 323 POAG patients. Of these 116 were patients who had HTG with intraocular perssure (IOP) >21mmHg and 207 were found to be non-HTG patients (presenting IOP<21mmHg). The study also included 303 participants as controls. The polymorphisms were genotyped in both the patients and the controls using the PCR-RFLP method. Moreover, the SNP that showed significant association was validated by DNA sequencing. The haplotypes were obtained using Haploview 4.1 software. The allele and haplotype frequencies were compared between the patient group and the control group using Pearson's ?(2) test. RESULTS: First, we genotyped the selected SNPs in the 323 POAG patients and 119 of the participants in the control group, in which only rs10038177 (c.710+30C>T) was found to be strongly associated with the HTG cases (OR=2.186; 95% CI=1.458-3.277; p=1.4×10(-4)). To increase the significance of the study, the SNP was genotyped in an additional 184 of the participants in the control group and it was observed that the SNP retained the association (OR=1.216; 95% CI=1.064-2.306; p=0.002). However, no haplotype was found to have any sustainable association with POAG. Based on the LD pattern and location of rs10038177, exon 5 of WDR36 was sequenced but no suspected disease-causing variant was detected. CONCLUSIONS: Our study suggests a possible association between WDR36 SNP in a cohort of eastern Indian POAG patients who also have high intraocular pressure (IOP). This study needs to be further validated in a larger patient cohort.

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

Progression of Primary Open-Angle Glaucoma in Diabetic and Nondiabetic Patients.

Publications

Progression of Primary Open-Angle Glaucoma in Diabetic and Nondiabetic Patients.

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