scholarly journals Lack of Association between Variant rs7916697 in ATOH7 and Primary Open Angle Glaucoma in a Saudi Cohort

2018 ◽  
Vol 2018 ◽  
pp. 1-6
Author(s):  
Altaf A. Kondkar ◽  
Taif A. Azad ◽  
Faisal A. Almobarak ◽  
Ibrahim M. Bahabri ◽  
Hatem Kalantan ◽  
...  

A case-control genetic association study was performed to investigate whether variant rs7916697 in atonal bHLH transcription factor 7 (ATOH7), which has been previously reported to be associated with optic disc parameters and primary open angle glaucoma (POAG) in different ethnic groups, is a risk factor for POAG or any of its clinical phenotypes in a Saudi cohort. Genotyping of rs7916697 (G>A) variant was performed in 186 unrelated POAG cases and 171 unrelated nonglaucomatous controls of Saudi origin using real-time Taq-Man® assay. Genotypic and allelic association with POAG and its related clinical indices were evaluated. Demographic and systemic disease status did not differ significantly between POAG cases and controls. Association analysis between POAG cases and controls showed no significant genotype effect under additive (p=0.707), dominant (p=0.458), and recessive (p=0.554) models. Besides, the minor ‘A’ allele frequency was 0.39 in POAG cases and 0.36 in controls with no significant distribution (p=0.406). In addition, there was no significant difference between genotypes and clinical phenotypes such as intraocular pressure and cup/disc ratio within the POAG group, or any age and sex adjusted genotype effect on the disease outcome in regression analysis. Variant rs7916697 in ATOH7 is not associated with POAG or its clinical indices such as IOP and cup/disc ratio in a Saudi cohort.

2021 ◽  
Vol 12 ◽  
Author(s):  
Altaf A. Kondkar ◽  
Taif A. Azad ◽  
Abdullah S. Alobaidan ◽  
Tahira Sultan ◽  
Essam A. Osman ◽  
...  

Objective: Recent studies have demonstrated an association of single nucleotide polymorphisms (SNPs) rs35934224 in TXNRD2 and rs6478746 near LMX1B genes in primary open-angle glaucoma (POAG) among Europeans. We performed a retrospective, case-control study to investigate the association between the rs35934224 (TXNRD2) and rs6478746 (LMX1B) and POAG in a middle-eastern population from Saudi Arabia.Methods: DNA from 399 participants consisting of 150 POAG cases (83 males and 67 females) and 249 controls (135 males and 114 females) were genotyped using TaqMan® real-time PCR. Statistical tests were performed to evaluate genetic association with POAG and related clinical indices.Results: The minor allele frequency (MAF) of rs35934224[T] was 0.19 and 0.20 in POAG and controls, respectively. The difference was non-significant (odds ratio [OR] = 1.08, 95% confidence interval [CI] = 0.75–1.55, p = 0.663). Likewise, rs6478746[G] MAF was 0.12 in both cases and controls with no statistical significance (OR = 1.02, 95% CI = 0.67–1.56, p = 0.910). Genotype analysis showed no association with POAG for both the SNPs in combined and gender-stratified groups. Regression analysis showed no significant effect of risk factors such as age, sex, rs35934224, and rs6478746 genotypes on POAG outcome. Furthermore, both the SNPs showed no significant genotype effect on clinical indices such as intraocular pressure (IOP) and cup/disc ratio in POAG patients.Conclusions: Rs35934224 in TXNRD2 and rs6478746 near LMX1B genes are not associated with POAG or related clinical indices such as IOP and cup/disc ratio in a Saudi cohort. Since the study is limited by sample size further investigations are needed to confirm these results in a larger cohort.


2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Altaf A. Kondkar ◽  
Taif A. Azad ◽  
Tahira Sultan ◽  
Essam A. Osman ◽  
Faisal A. Almobarak ◽  
...  

Purpose. To determine the association between plasma 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels, a marker for oxidative DNA damage, and patients with primary open-angle glaucoma (POAG) or its clinical phenotypes. Furthermore, we also examined the utility of plasma 8-OHdG as a potential biomarker in POAG. Materials and Methods. In a retrospective case-control study, plasma samples were obtained from 50 POAG cases and 45 glaucoma-free controls matched for age, sex, and ethnicity. 8-OHdG levels were measured in duplicate using an enzyme-linked immunosorbent assay (ELISA) on an automated ELISA analyzer. Results. There was no significant difference in age, sex, and systemic disease distribution between POAG cases and controls. Both mean and median 8-OHdG levels were significantly elevated in POAG cases and male subjects. The area under the receiver operating characteristic (ROC) curve value for plasma 8-OHdG was 0.653 (95% confidence interval = 0.54–0.76, p=0.010). The cutoff values based on quartile distribution and ROC curve analysis showed that elevated plasma 8-OHdG significantly increased the risk of POAG by more than 4-folds. Plasma 8-OHdG had a sensitivity of 78% and specificity of 53%. In logistic regression analysis, 8-OHdG showed a significant effect on POAG outcome (p=0.016) independent of age, sex, smoking, and systemic diseases. However, no significant correlation was observed between 8-OHdG and specific clinical markers of glaucoma such as intraocular pressure (p=0.699), cup/disc ratio (p=0.213), and the number of antiglaucoma medications (p=0.603). Conclusion. The study shows that there is a significant association between elevated plasma 8-OHdG and POAG, supporting the role of systemic oxidative stress-induced DNA damage in POAG pathogenesis. However, with a high rate of false-positivity, plasma 8-OHdG may lack the ability to serve as a potential biomarker in POAG. Further studies in a much larger cohort are needed to confirm these findings.


2019 ◽  
Vol 76 (8) ◽  
pp. 822-829
Author(s):  
Vesna Maric ◽  
Vujica Markovic ◽  
Marija Bozic ◽  
Ivan Marjanovic ◽  
Paraskeva Hentova-Sencanic ◽  
...  

Background/Aim. Trabeculectomy is a safe procedure which effectively reduces the intraocular pressure (IOP). IOP is the most frequent indicator of success after glaucoma surgery. The aim of this work was to evaluate the long-term pressure control in primary open-angle glaucoma (POAG) and in pseudoexfoliative glaucoma (XFG) after primary trabeculectomy without the use of mitomycin-C (MMC), 3 to 5 years after trabeculectomy. Methods. This study involved a retrospective evaluation of 332 consecutive patients (352 eyes), 174 patients (188 eyes) with POAG (mean age of 64.0 ? 8.6 years) and 158 patients (164 eyes) with XFG (mean age of 70.7 ? 8.9 years) who underwent primary trabeculectomy between January 2007 and December 2009 at the Clinic for Eye Diseases, Clinical Center of Serbia in Belgrade. A successful control of IOP was defined as achieving IOP ? 21 mmHg without medication (complete success), or with a single topical medication (qualified success). Results. According to the type of glaucoma POAG/XFG preoperative IOP was 28.4 ? 6.3/30.4 ? 8.4 mmHg, respectively (p = 0.311) and last postoperative IOP was 16.9 ? 5.2/18.7 ? 5.9 mmHg, respectively (p = 0.681). According to the Kaplan-Meier survival curve, the complete success in the group with POAG in 1, 3 and 5 years were 85%, 75% and 58% and in the group with XFG were 82%, 70% and 56%, respectively. There was no statistically significant difference in the complete success rates between the patients with POAG and XFG. Conclusion. The primary goal of surgery was to achieve a sufficiently low IOP without additional medication, thus preventing progression of glaucomatous damage. In our study, the complete success in the group with POAG was achieved in 75% and 58% of the patients in the period of 3 and 5 years after surgery, respectively and in the group with XFG complete success was achieved in 70% and 56% of the patients respectively.


2021 ◽  
Author(s):  
Giorgia Demaria ◽  
Azzurra Invernizzi ◽  
Daniel Ombelet ◽  
Joana Carvalho ◽  
Remco Renken ◽  
...  

Recent brain imaging studies have shown that the degenerative eye damage generally observed in the clinical setting, also extends intracranially. Both structural and functional brain changes have been observed in glaucoma participants, but we still lack an understanding of whether these changes also affect the integrity of cortical functional networks. This is relevant, as functional network integrity may affect the applicability of future treatments, as well as the options for rehabilitation or training. Here, we compare global and local functional connectivity between glaucoma and controls. Moreover, we study the relationship between functional connectivity and visual field (VF) loss. For our study, 20 subjects with primary open angle glaucoma (POAG) and 24 age similar healthy participants were recruited to undergo a complete ophthalmic assessment followed by two resting state (RS) (f)MRI scans. For each scan and for each group, the ROIs with EC values higher than the 95th percentile were considered the most central brain regions (hubs). Hubs for which we found a significant difference in EC in both scans between glaucoma and healthy were considered to provide evidence for network changes. In addition, for each participant, behavioural scores were derived based on the notion that a brain regions hub function might relate to the: 1) sensitivity of the worse eye, indicating disease severity, 2) sensitivity of both eyes combined, with one eye potentially compensating for loss in the other, or 3) difference in eye sensitivity, requiring additional network interactions. By correlating each of these VF scores and the EC values, we assessed whether VF defects could be associated with centrality alterations in POAG. Our results show that no functional connectivity disruptions were found at the global brain level in POAG participants. This indicates that in glaucoma global brain network communication is preserved. Furthermore, a positive correlation was found between the EC value of the Lingual Gyrus, identified as a brain hub, and the behavioral score for the VF sensitivity of both eyes combined. The fact that reduced local network functioning is associated with reduced binocular VF sensitivity suggests the presence of local brain reorganization that has a bearing on functional visual abilities.


2019 ◽  
Vol 30 (3) ◽  
pp. 513-524
Author(s):  
Vesna D Maric ◽  
Anita D Grgurevic ◽  
Andja M Cirkovic ◽  
Ivan S Marjanovic ◽  
Marija M Bozic

Purpose: To evaluate the clinical characteristics of newly diagnosed pseudoexfoliative glaucoma and compare them with those pertaining to newly diagnosed primary open-angle glaucoma as well as pseudoexfoliation syndrome. Methods: This case–control study involved 306 participants, including patients with newly diagnosed pseudoexfoliative glaucoma, age- and sex-matched normal controls, patients with newly diagnosed primary open-angle glaucoma, and subjects with pseudoexfoliation syndrome. The study was conducted at the Glaucoma Department of Clinic for Eye Diseases, Clinical Center of Serbia, as the referral center for glaucoma in Serbia. Results: The mean age in the pseudoexfoliative glaucoma, primary open-angle glaucoma, pseudoexfoliation syndrome, and normal control groups was 73.61 ± 8.46, 65.50 ± 8.97, 74.81 ± 6.80, and 73.58 ± 9.34 years, respectively (pseudoexfoliative glaucoma vs primary open-angle glaucoma, p < 0.001). Unilateral pseudoexfoliative glaucoma was diagnosed in 35 patients (42.2%). The intraocular pressure was higher in the eyes affected by pseudoexfoliative glaucoma (32.0 ± 9.5 mmHg) than that in the primary open-angle glaucoma eyes (28.8 ± 5.9 mmHg) (p < 0.001). In pseudoexfoliative glaucoma and primary open-angle glaucoma eyes, glaucoma severity was determined via the vertical cup-to-disk ratio (C/D) 0.65 (0.45–1.0) versus 0.60 (0.45–1.0), p = 0.048 and visual field mean deviation −5.68 (−1.58 to −30.9) versus −4.70 (−1.39 to −31.0), p = 0.045. Alzheimer’s was the only systemic disease associated with pseudoexfoliative glaucoma in the study sample, with an odds ratio of 0.021 (95% confidence interval = 0.00−21.52, p = 0.022). Conclusion: At the time of diagnosis, pseudoexfoliative glaucoma exhibits different clinical features compared with primary open-angle glaucoma. Higher intraocular pressure, narrow or occludable angle, increased trabecular pigmentation, phacodonesis, and poorer pupillary dilatation emerged as the factors associated with pseudoexfoliative glaucoma.


Author(s):  
Olha V. Levytska ◽  
Igor Ya. Novytskyy

Hypotensive effect of endotrabeculectomy was compared with that of selective laser trabeculoplasty in patients with primary open-angle glaucoma (POAG). We evaluated 44 patients (44 eyes) with POAG. In the first group (23 patients), endotrabeculectomy (trabecular ablation through the angle of anterior chamber) was performed, and in the second group (21 patients) the patients underwent selective laser trabeculoplasty. When comparing the intraocular pressure (IOP), it was found that the difference between preoperative and postoperative IOP was significant up to 6 months of follow-up in both groups (p < 0.05), however, hypotensive effect in the first group was more pronounced (7.58 vs. 1.55 mmHg, respectively). When comparing the number of hypotensive medications used before and after glaucoma surgery, it was found that the difference in patients of the first group was significant throughout the observation period (p = 0.028), while in patients of the second group there was no significant difference from the 3rd month of observation. The number of topical drugs to reduce IOP decreased by 1.44 in the first group (p < 0.05) and by 0.33 in the second group (p = 0.109). Endotrabeculectomy, as well as selective laser trabeculoplasty, showed significant hypotensive effect in patients with POAG within 6 months of observation, however, hypotensive effect of endotrabeculectomy significantly overweighted that of SLT. Keywords: endotrabeculectomy, selective laser trabeculoplasty, intraocular pressure, primary open-angle glaucoma.


2013 ◽  
Vol 33 (2) ◽  
pp. 143-148 ◽  
Author(s):  
Mohammad Najafi ◽  
Morteza Nouruzi Yeganeh ◽  
Arezoo Miraftabi ◽  
Reza Zarei ◽  
Isa Noormohammadi

Summary Background Glaucoma is a highly prevalent eye disease related to optic nerve lesions and visual field defects. Primary Open-Angle Glaucoma (POAG) is a type of glaucoma that occurs frequently with unknown etiology. In this study, we investigated the serum levels of selenium, selenoprotein P1, glutathione, hemolysate glutathione peroxidase1 (GPx1) activity and aqueous humour selenium in POAG patients. Methods Ninety sex- and age-matched subjects (POAG patients; n=45 and, controls; n=45) with the controlled confounders (smoking, hypertension and alcohol beverages) were recruited on clinical histories and exams. The serum and aqueous humour selenium levels were measured using GFAAS technique. The serum selenoprotein P1 level was assayed with the ELISA method. The hemolysate GPx1 activity and serum reduced glutathione level were also measured using known colorimetric techniques. Results The serum selenium (P=0.01) and selenoprotein P1 (P<0.001) levels were significantly high in POAG patients. Furthermore, the aqueous humour selenium level was significantly high among patients as compared to controls (64.68±13.07 vs. 58.36±13.76 ng/mL, P=0.02). The results did not show a significant difference (P=0.36) in the hemolysate GPx1 activity between the groups. The cutoff points for intraocular pressure (IOP) and serum selenoprotein P1 parameters were estimated to be 39 mmHg (sensitivity 97.5%; 1-specificity 6.5%) and 188 mg/mL (sensitivity 93.5%; 1-specificity 14%), respectively.


2018 ◽  
Vol 243 (13) ◽  
pp. 1083-1091 ◽  
Author(s):  
Mariana B Oliveira ◽  
José Paulo C de Vasconcellos ◽  
Galina Ananina ◽  
Vital P Costa ◽  
Mônica B de Melo

The aim of this study was to investigate the association of five polymorphisms in the IL1A and IL1B genes in Brazilian patients with primary open angle glaucoma (POAG). A case–control study, including 214 unrelated POAG patients and 187 healthy individuals, was conducted to evaluate the frequency of polymorphisms in the IL1A and IL1B genes. Ophthalmic evaluation was performed and genomic DNA was obtained from all participants. Five single nucleotide polymorphisms (SNPs): IL1A (–889C/T: rs1800587:C > T, +4845G/T:rs17561G>T) and IL1B (–31C/T:rs1143627:T > C, –511C/T:rs16944C>T and +3954C/T:rs1143634:C > T) were genotyped through direct sequencing. The association of individual SNPs was tested using logistic regression. There was an association between the –31C/T and –511 C/T polymorphisms in the IL1B gene with POAG (p = 0.002 and p = 0.009, respectively). High linkage disequilibrium was observed between the –31C/T and –511C/T polymorphisms. The statistical analysis showed that the T/C haplotype (–31/–511) in the IL1B gene is more frequent in controls (p = 0.011) and the C/T haplotype (–31/–511) is more common in POAG patients (p = 0.018). Among POAG cases, the genotypic distribution of the –31C/T and –511 C/T SNPs was significantly different in patients who underwent anti-glaucomatous surgery compared to patients without surgery (p = 0.016 and 0.023, respectively). There was no statistically significant difference for the remaining SNPs between POAG patients and controls. In conclusion, the C allele of the –31C/T and the T allele of the –511C/T polymorphisms in the IL1B gene may represent a “risk haplotype” for the development of POAG in Brazilian individuals. Further studies with larger cohorts of patients are necessary to substantiate these findings. Impact statement This study is the first, according to our knowledge, to show the association between glaucoma and the functional –31C/T single nucleotide polymorphism. We provide evidence indicating that homozygotes CC at –31C/T and TT at –511 C/T of IL1B are at risk for glaucoma. We also demonstrated that these polymorphisms are in strong linkage disequilibrium (LD). Increasing evidence support the role of inflammation in glaucoma and this study is an important result that reinforces these findings. How IL-1 signaling influences the triggering and pathogenesis of glaucoma remains to be investigated. Greater understanding of the mechanisms leading to glaucoma will provide the development of new management strategies that target the primary disease lesion and maybe the discovery of new treatments.


2014 ◽  
Vol 7 (1) ◽  
pp. 19-27 ◽  
Author(s):  
R. V. Avdeyev ◽  
A. S. Aleksandrov ◽  
A. S. Basinskiy ◽  
Ye. A. Blyum ◽  
A. Yu. Brezhnev ◽  
...  

A study of cross-impact degree and morpho-functional correlation characteristics of primary open angle glaucoma and age-related macular degeneration was performed at 25 clinical sites in Russia and some CIS countries from January through May 2013. The study final protocol included 87 patients (108 eyes) divided into two groups, mean age of patients was 66.6 ± 5.65 years (min 55; max 81). Intragroup and intergroup variance analysis did not establish any significant difference in the macular area between the «glaucoma» group and the «glaucoma + AMD» group depending on the disease stage. The findings suggest that macular degeneration develops subsequent to a preexisting glaucomatous state.


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