Primary Open-angle Glaucoma Cases Research Articles

Elevated Plasma Level of 8-Hydroxy-2'-deoxyguanosine Is Associated with Primary Open-Angle Glaucoma.

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.

Low-carbohydrate-diet scores and the risk of primary open-angle glaucoma: data from three US cohorts.

Background/objectivesTo assess the long-term association between low-carbohydrate dietary patterns and incident primary open-angle glaucoma (POAG), and POAG subtypes defined by highest untreated intraocular pressure (IOP) and by pattern of visual field (VF) loss at diagnosis.Subjects/methodsWe followed 185,638 participants of three large US prospective cohorts biennially (1976–2016, 1986–2016 and 1991–2017). Deciles of three low-carbohydrate-diet scores were calculated to represent adherence to diets lower in carbohydrate and higher in protein and fat from any source, animal sources or plant sources. We confirmed POAG cases (n = 2112) by medical record review and used Cox proportional hazards models to estimate multivariable-adjusted relative risks (MVRRs) and 95% confidence intervals (CIs).ResultsThere was no association between the three types of low-carbohydrate-diet scores and POAG: the MVRR for POAG in the highest vs. lowest deciles was 1.13 (95% CI, 0.91–1.39; Ptrend = 0.40) for the overall score; 1.10 (95% CI, 0.89–1.35; Ptrend = 0.38) for the animal score and 0.96 (95% CI, 0.79–1.18; Ptrend = 0.88) for the vegetable score. No differential associations by IOP level was found (Pheterogeneity ≥ 0.06). However, the vegetable score showed a suggestive inverse association with early paracentral VF loss (highest vs. lowest decile MVRR = 0.78 [95% CI, 0.55–1.10]; Ptrend = 0.12) but not with peripheral VF loss only (MVRR = 1.09 [95% CI, 0.83–1.44]; Ptrend = 0.14; Pheterogeneity = 0.03).ConclusionsLow-carbohydrate diets were not associated with risk of POAG. Our data suggested that higher consumption of fat and protein from vegetable sources substituting for carbohydrates was associated with lower risk of the POAG subtype with initial paracentral VF loss.

Association of endothelial nitric oxide synthase (NOS3) gene polymorphisms with primary open-angle glaucoma in a Saudi cohort

AimTo investigate the association of endothelial nitric oxide synthase (NOS3) gene polymorphisms in patients with primary open-angle glaucoma (POAG) of Saudi origin.MethodsThis case-control study included 173 patients with POAG (94 men and 79 women) and 171 controls (98 men and 73 women). Genotyping of rs2070744 (T-786C) and rs1799983 (G894T) variants of the NOS3 gene was performed using TaqMan® assay.ResultsRs1799983 genotypes showed a significant association with POAG but did not survive Bonferroni correction (pcorrection = 0.01). The minor ‘T’ allele was significantly associated with the risk of POAG among men (p = 0.025, odds ratio (OR) = 1.77, 95% confidence interval (CI) = 1.07–2.94). Likewise, the genotypes were significantly associated with POAG among men in dominant (p = 0.030, OR = 1.92, 95% CI = 1.06–3.48) and log-additive models (p = 0.022, OR = 1.82, 95% CI = 1.08–3.07), and after adjustment for age and smoking. Genotype and allele frequencies of rs2070744 were not significantly different between POAG cases and controls, and after sex stratification. CG haplotype was significantly protective (p = 0.011, OR = 0.52, 95% CI = 0.32–0.87) and CT haplotype conferred significantly increased risk of POAG (p = 0.016, OR = 2.60, 95% CI = 1.16–5.82) among men. Rs1799983 showed trend (p = 0.054) towards risk of POAG independent of age, gender, smoking, and rs2070744 polymorphism in logistic regression analysis. Both the polymorphisms showed no association with POAG phenotypes such as intraocular pressure and cup/disc ratio.ConclusionOur results suggest that the polymorphism rs1799983 and the haplotypes of rs20707440 and rs1799983 in the NOS3 gene may significantly modulate the risk of POAG in Saudi’s, particularly among men. Further larger studies are needed to confirm these findings.

CHANGES IN GANGLION CELL AND INNER PLEXIFORM LAYERS THICKNESS AND RETINAL MICROVASCULATURE IN DIFFERENT STAGES OF GLAUCOMA

Background: Primary open angle glaucoma (POAG) is an optic neuropathy characterized by progressive degeneration of retinal ganglion cells (RGC) and their axons, which results in characteristic excavation of the neuroretinal rim with corresponding visual field (VF) deficits. Optical coherence tomography angiography (OCTA) is a novel imaging modality that can detect vascular flow of the retina and choroid in great detail. The ability to segment OCT angiograms into the different vascular layers may improve understanding of disease pathogenesis. Objective: To evaluate the correlation between Ganglion Cell and Inner Plexiform Layers thickness using optical coherence tomography (OCT) and the macular microvasculature density in different stages of primary open angle glaucoma using optical coherence tomography angiography (OCTA). Subjects and Methods: The study was performed on 80 eyes of 48 subjects including 20 eyes of 11 controls, and 60 eyes of 37 POAG cases which were divided into 3 groups according to Hodapp,Parish,Anderson (H-P-A) classification; Group1: mild glaucoma (20 eyes), Group 2: moderate glaucoma (20 eyes),Group 3: severe glaucoma (20 eyes). Results: In our study, we found that there was a significant reduction in Ganglion Cell - Inner Plexiform Layer (GCIPL) thickness and macular VD in patients with POAG which increased with increasing glaucoma severity, also we found that OCT and OCTA parametrs were significantly differentiate between normal and POAG cases and also between different stages of POAG. Also we found that an OCTA was an important diagnostic tool in diagnosing mild cases of POAG and to differentiate between mild and moderate cases of POAG,in contrast to OCT in which there was no significant differance between mild and moderate cases of POAG. OCTA seems to be a good candidate for diagnosis and follow-up of glaucoma, complementing the results provided by OCT and visual field testing. Conclusion: Significant differences between eyes with POAG and normal eyes in terms of the macular GCIPL thickness and microvasculature density (VD) suggest that the macular GCIPL thickness and the retinal capillary vessel area density may be reliable indicators of glaucoma severity.

Correlation of open-angle glaucoma and ocular perfusion pressure in hypertensive individuals

Background: Systemic hypertension has been recognized as a potential risk factor for primary open-angle glaucoma (POAG). Purpose: The purpose of this study is to study the correlation of systemic blood pressure, intraocular pressure (IOP), and ocular perfusion pressure (OPP) for the development of glaucoma in hypertensive individuals. Methods: After Institutional Ethics Committee approval, a hospital-based case–control study was conducted in a tertiary care hospital. The study group comprised of patients with systemic hypertension, and the control group had the age- and sex-matched normotensives. POAG was diagnosed if glaucomatous cupping and characteristics visual field defects were present with open angles on gonioscopy. OPP was compared between POAG and non-POAG groups. Results: In this study of 103 hypertensive and 100 normotensive patients, the mean IOP was higher among hypertensives. There were 9 (8.74%) cases of POAG in hypertensive group and 2 (2%) in the normotensive group. The mean IOP in hypertensive group was 16.5 ± 4.5 mmHg, and that of normotensive group was 13.14 ± 3.19 mmHg. The mean OPP in hypertensive patients with glaucoma was 49.38 ± 2.6 mmHg, which was significantly lower than that of patients without glaucoma, i.e., 60.16 ± 5.42 mmHg, as indicated by P < ,0.001. Conclusion: This study reveals that hypertensive patients taking anti-HT treatment with POAG have lower mean OPP as compared to those without POAG. The higher OPP could be protective against glaucomatous condition; however, interdisciplinary management of open-angle glaucoma and hypertension is the need for a better quality of life of such patients.

CHANGES IN GANGLION CELL AND INNER PLEXIFORM LAYERS THICKNESS AND RETINAL MICROVASCULATURE IN DIFFERENT STAGES OF GLAUCOMA

Background: Primary open angle glaucoma (POAG) is an optic neuropathy characterized by progressive degeneration of retinal ganglion cells (RGC) and their axons, which results in characteristic excavation of the neuroretinal rim with corresponding visual field (VF) deficits. Optical coherence tomography angiography (OCTA) is a novel imaging modality that can detect vascular flow of the retina and choroid in great detail. The ability to segment OCT angiograms into the different vascular layers may improve understanding of disease pathogenesis. Objective: To evaluate the correlation between Ganglion Cell and Inner Plexiform Layers thickness using optical coherence tomography (OCT) and the macular microvasculature density in different stages of primary open angle glaucoma using optical coherence tomography angiography (OCTA). Subjects and Methods: The study was performed on 80 eyes of 48 subjects including 20 eyes of 11 controls, and 60 eyes of 37 POAG cases which were divided into 3 groups according to Hodapp,Parish,Anderson (H-P-A) classification; Group1: mild glaucoma (20 eyes), Group 2: moderate glaucoma (20 eyes),Group 3: severe glaucoma (20 eyes). Results: In our study, we found that there was a significant reduction in Ganglion Cell - Inner Plexiform Layer (GCIPL) thickness and macular VD in patients with POAG which increased with increasing glaucoma severity, also we found that OCT and OCTA parametrs were significantly differentiate between normal and POAG cases and also between different stages of POAG. Also we found that an OCTA was an important diagnostic tool in diagnosing mild cases of POAG and to differentiate between mild and moderate cases of POAG,in contrast to OCT in which there was no significant differance between mild and moderate cases of POAG. OCTA seems to be a good candidate for diagnosis and follow-up of glaucoma, complementing the results provided by OCT and visual field testing. Conclusion: Significant differences between eyes with POAG and normal eyes in terms of the macular GCIPL thickness and microvasculature density (VD) suggest that the macular GCIPL thickness and the retinal capillary vessel area density may be reliable indicators of glaucoma severity.

Prevalence of Primary Open Angle Glaucoma among Patients with Diagnosis of Systemic Hypertension and Diabetes Mellitus: The Colombian Glaucoma Study

Objective: To establish the prevalence and risk factors of Primary Open Angle Glaucoma (POAG) among patients with Systemic Hypertension (SH) and Diabetes Mellitus (DM) in six cities of Colombia. Methods: A cross-sectional study among hypertensive and diabetic patients was conducted in Colombia. This study included 2067 subjects older than 50 years of age diagnosed with SH and/or DM. Participants underwent a complete ophthalmic examination including intraocular pressure (IOP) measurement by Goldmann tonometry and blood pressure measurement. The glaucoma diagnosis was confirmed by structural and functional evidence. Interviews and standardized questionnaires were used to evaluate participants’ lifestyle and other health conditions. Results: Among participants with DM/SH, 142 cases of POAG were confirmed for a prevalence of 5.6% [95% CI: 4.6 - 6.6], while 9.1% were glaucoma suspects [95% CI: 7.8% - 10.4%]. The majority of confirmed cases (77.5%) were undiagnosed. The prevalence of POAG was significantly higher with male gender, greater age, and diastolic blood pressure > 90 mmHg as risk factors. Conclusion: We found a high prevalence of POAG in patients with adequate SH and DM care in a novel Latino population. We also found great unawareness of the disease in this population. Our results have potentially enormous public health implications for Colombia and other Latino populations.

Association of Systemic Medication Exposure With Glaucoma Progression and Glaucoma Suspect Conversion in the Groningen Longitudinal Glaucoma Study.

To determine the association of statins, five classes of antihypertensive medications, and proton pump inhibitors with (1) primary open-angle glaucoma (POAG) progression and (2) conversion of POAG suspects to POAG. We retrospectively investigated the records of a cohort with POAG cases and suspects from the Groningen Longitudinal Glaucoma Study. To quantify visual field (VF) deterioration in cases, we used the rate of progression of the mean deviation (MD). Suspects were considered to have converted at the time point after which two consecutive VF tests for at least one eye were abnormal (glaucoma hemifield test outside normal limits). Progression and conversion were analyzed with quantile and logistic regression, respectively, with the systemic medications as predictors, controlling for age, sex, body mass index, pretreatment IOP, corneal thickness, and baseline MD. The multivariable models were built with and without IOP intervention. No systemic medications were associated with POAG progression in the final IOP/treatment-adjusted or unadjusted model. However, angiotensin II receptor blockers (ARBs) appeared to slow progression in older patients (b = 0.014, P = 0.0001). Angiotensin-converting enzyme inhibitors (ACEIs) were significantly associated with a decrease in POAG suspect conversion in both the IOP/treatment-adjusted and -unadjusted model (odds ratio [OR] 0.23, 95% confidence interval [CI] 0.07-0.79, P = 0.012; OR=0.24, 95% CI 0.07-0.78, P = 0.021, respectively), as were ARBs (OR 0.12, 95% CI 0.01-0.98, P = 0.014; OR 0.11, 95% CI 0.01-0.87, P = 0.005, respectively). No overall association of VF progression with systemic medication was found; ARBs delayed progression in older patients. ACEIs and ARBs were associated with lower risk of suspect conversion. The pathophysiology of this relationship is to be disentangled.

Primary Open-Angle African American Glaucoma Genetics (POAAGG) Study: gender and risk of POAG in African Americans.

The purpose of this study was to investigate the association between gender and primary open-angle glaucoma (POAG) among African Americans and to assess demographic, systemic, and behavioral factors that may contribute to differences between genders. The Primary Open-Angle African American Glaucoma Genetics (POAAGG) study had a case-control design and included African Americans 35 years and older, recruited from the greater Philadelphia, Pennsylvania. Diagnosis of POAG was based on evidence of both glaucomatous optic nerve damage and characteristic visual field loss. Demographic and behavioral information, history of systemic diseases and anthropometric measurements were obtained at study enrollment. Gender differences in risk of POAG were examined using multivariate logistic regression. A total of 2,290 POAG cases and 2,538 controls were included in the study. The percentage of men among cases was higher than among controls (38.6% vs 30.3%, P<0.001). The subjects’ mean age at enrollment was significantly higher for cases compared to controls (70.2±11.3 vs. 61.6±11.8 years, P<0.003). Cases had lower rates of diabetes (40% vs. 46%, P<0.001), higher rates of systemic hypertension (80% vs. 72%, P<0.001), and lower body mass index (BMI) (29.7±6.7 vs. 31.9±7.4, P<0.001) than controls. In the final multivariable model, male gender was significantly associated with POAG risk (OR, 1.64; 95% CI, 1.44–1.87; P<0.001), after adjusting for age, systemic hypertension, diabetes, and BMI. Within the POAAGG study, men were at higher risk of having POAG than women. Pending genetic results from this study will be used to better understand the underlying genetic variations that may account for these differences.

Familial primary open-angle glaucoma: A case report

Glaucoma affects more than 70 million people worldwide with approximately 10% being bilaterally blind, making it the leading cause of irreversible blindness in the world. Primary open-angle glaucoma (POAG) is a disease that is often inherited. We reported a case of Primary open-angle glaucoma in 27 years old male patient.

Determining Possible Shared Genetic Architecture Between Myopia and Primary Open-Angle Glaucoma.

PurposeTo determine genetic correlations between common myopia and primary open-angle glaucoma (POAG).MethodsWe tested the association of myopia polygenic risk scores (PRSs) with POAG and POAG endophenotypes using two studies: the Australian & New Zealand Registry of Advanced Glaucoma (ANZRAG) study comprising 798 POAG cases with 1992 controls, and the Rotterdam Study (RS), a population-based study with 11,097 participants, in which intraocular pressure (IOP) and optic disc parameter measurements were catalogued. PRSs were derived from genome-wide association study meta-analyses conducted by the Consortium for Refractive Error and Myopia (CREAM) and 23andMe. In total, 12 PRSs were constructed and tested. Further, we explored the genetic correlation between myopia, POAG, and POAG endophenotypes by using the linkage disequilibrium score regression (LDSC) method.ResultsWe did not find significant evidence for an association between PRS of myopia with POAG (P = 0.81), IOP (P = 0.07), vertical cup–disc ratio (P = 0.42), or cup area (P = 0.25). We observed a nominal association with retinal nerve fiber layer (P = 7.7 × 10−3) and a significant association between PRS for myopia and disc area (P = 1.59 × 10−9). Using the LDSC method, we found a genetic correlation only between myopia and disc area (genetic correlation [RhoG] = −0.12, P = 1.8 × 10−3), supporting the findings of the PRS approach.ConclusionsUsing two complementary approaches we found no evidence to support a genetic overlap between myopia and POAG; our results suggest that the comorbidity of these diseases is not influenced by common variants. The association between myopia and optic disc size is well known and validates this methodology.

Frequencies of 4 Distinct Patterns of Glaucomatous Disc Appearance and Their Clinical Associations in Japanese Population-based Studies

To study the frequencies and factors associated with 4 disc patterns in primary open-angle glaucoma (POAG) identified in population-based studies: focal glaucomatous (FG type), generalized enlargement of cup (GE type), myopic glaucomatous (MG type), and senile sclerotic glaucomatous (SS type) patterns. In total, 270 disc photographs of acceptable quality were extracted from the records of 270 definitive POAG cases diagnosed according to the International Society of Geographical and Epidemiological Ophthalmology Criteria in 2 Japanese population-based glaucoma surveys. One randomly chosen eye from the bilateral POAG cases was included. Using a method of κ coefficient of reproducibility of classification of 0.80 according to a preliminary study, 143 discs were classified as FG, GE, MG, or SS types with respective frequencies of 57% (95% confidence interval [CI], 48-66), 33% (95% CI, 25-42), 7% (95% CI, 3-13), and 3% (95% CI, 0-7), and 127 discs as the miscellaneous type. Multinomial logistic regression analysis showed that the MG type was associated (P=0.052, 0.025, 0.019, and 0.018) with younger age, lower body mass index (BMI), and greater disc area and ovality, and the GE type was associated (P<0.001, 0.036, and 0.056) with greater disc area, corneal radius, and hyperopic refraction than the FG type. The FG type occurs most frequently in Japanese POAG followed by the GE type. The MG and SS types occurred much less often than previously reported in Japanese. Associations with age, BMI, disc area and ovality, refraction, and corneal radius differed among the FG, GE, and MG types.

Inflammatory model in patients with primary open angle glaucoma and diabetes

To assess the inflammatory cytokines expression in aqueous humor in diabetic primary open angle glaucoma (POAG) patients. A cross-sectional study on 87 eyes, distributed as following: 26 eyes from diabetic patients, 16 eyes with POAG and 21 eyes from diabetic POAG patients; healthy controls (24 eyes) were recruited from patients undergoing conventional cataract surgery. A volume of 100 µL of aqueous humor (AH) was collected during phacoemulsification and 21 inflammatory markers were quantified using a Luminex® cytometric bead assay: IL-1Ra, IL-1α, IL-1β, IL-5, IL-6, IL-10, IL-17, GM-CSF, IFNγ, CCL2, CCL3, CCL4, CXCL5, CXCL8, bFGF, VEGF, TNFα. Main changes in cytokine profile were analyzed and compared between groups. Data on demographics, duration of glaucoma, intraocular pressure (IOP), number of anti-glaucoma substances were recorded for correlation analysis and prediction models. Significant differences in cytokine expression between groups were detected for CXCL5 (P<0.001), CXCL8 (P=0.004), IL-1α (P<0.001), IL-2 (P<0.001), CCL4 (P=0.003), CCL5 (P<0.001) and TNFα (P=0.05). Post-hoc analysis identified IL-2 (P=0.009) and CXCL5 (P<0.001) as "separation markers" between POAG and diabetic POAG eyes. In POAG patients, the "separation markers" could highly predict the TNFα levels F(1, 16)=14.639, P<0.001, whereas in diabetic patients F(1, 24)=4.844, P=0.006 and diabetic POAG patients F(1, 19)=2.358, P=0.05 the level of prediction was inferior. Our results reveal an inflammatory model based on increased TNFα levels in POAG eyes. Simultaneous co-stimulatory molecules and additional inflammatory pathways need to be further explored in diabetic POAG cases, since the prediction model could only partially explain the increased TNFα level in this category of patients.

Association of Statin Use and High Serum Cholesterol Levels With Risk of Primary Open-Angle Glaucoma

The use of statins (hydroxymethylglutaryl coenzyme A inhibitors) has been associated with a lower risk of primary open-angle glaucoma (POAG); however, results have been conflicting, and little is known about the association between high cholesterol levels and POAG. To assess the association of elevated cholesterol levels and statin use with incident POAG. This study used data collected biennially from participants aged 40 years or older who were free of glaucoma and reported eye examinations, within 3 population-based cohorts: the Nurses' Health Study (N = 50 710; followed up from 2000 to 2014), the Nurses' Health Study 2 (N = 62 992; 1999-2015), and the Health Professionals Follow-up Study (N = 23 080; 2000-2014). Incident cases of POAG were confirmed by medical record review. The analyses were performed in January 2019. Biennially updated self-reported information on elevated cholesterol level status, serum cholesterol levels, and duration of statin use. Multivariable-adjusted relative risks (RRs) and 95% CIs were estimated using Cox proportional hazards regression models on pooled data, with stratification by cohort. Among the 136 782 participants in the 3 cohorts (113 702 women and 23 080 men), 886 incident cases of POAG were identified. Every 20-mg/dL increase in total serum cholesterol was associated with a 7% increase in risk of POAG (RR, 1.07 [95% CI, 1.02-1.11]; P = .004). Any self-reported history of elevated cholesterol was also associated with a higher risk of POAG (RR, 1.17 [95% CI, 1.00-1.37]). A history of any statin use was associated with a 15% lower risk of POAG (RR, 0.85 [95% CI, 0.73-0.99]). Use of statins for 5 or more years vs never use of statins was associated with a 21% lower risk of POAG (RR, 0.79 [95% CI, 0.65-0.97]; P = .02 for linear trend). The association between use of statins for 5 or more years vs never use of statins and risk of POAG was more inverse in those who were older (≥65 years: RR, 0.70 [95% CI, 0.56-0.87] vs <65 years: RR, 1.05 [95% CI, 0.68-1.63]; P = .01 for interaction). Among adults aged 40 years or older, higher serum cholesterol levels were associated with higher risk of POAG, while 5 or more years of statin use compared with never use of statins was associated with a lower risk of POAG.

Evaluation of dynamic thiol-disulfide homeostasis in glaucoma patients and the correlation with retinal nerve fiber layer analysis.

The aim of this study was to evaluate thiol/disulfide homeostasis and ischemia-modified albumin levels with primary open-angle glaucoma, ocular hypertension, and control group; also to interpret the correlation between these biochemical parameters and retinal nerve fiber layer analysis. In a prospective cross-sectional study, 30 primary open-angle glaucoma cases, 30 ocular hypertension cases, and 30 control subjects were included in the study. Native thiol, total thiol, and disulfide measurements and disulfide/native thiol, disulfide/total thiol, and native thiol/total thiol ratios were evaluated as thiol-disulfide homeostasis. Albumin and ischemia-modified albumin parameters were also evaluated. All cases underwent detailed ophthalmologic examination including visual acuity, retinal nerve fiber layer via optical coherence tomography, intraocular pressure, and central corneal thickness measurements and visual field analysis by 24-2 Swedish Interactive Threshold Algorithm (SITA) Standard visual field test. Primary open-angle glaucoma group had significantly higher ischemia-modified albumin values than ocular hypertension and control group (p < 0.001). Native thiol and total thiol values of control group were statistically higher than those of primary open-angle glaucoma and ocular hypertension groups. The correlation between the temporal retinal nerve fiber layer value and ischemia-modified albumin, disulfide/native thiol, and disulfide/total thiol values of the primary open-angle glaucoma patients included in the study was moderate correlation in negative direction (r = -0.46, r = -0.39, r = -0.39, respectively), whereas there was a statistically significant moderate correlation in positive direction between the native thiol/total thiol values (r = 0.39) (p < 0.05). These findings have reinforced the role of oxidative stress in the etiopathogenesis of primary open-angle glaucoma, suggesting that the thinning retinal nerve fiber layer may be associated with oxidative stress in favor of prooxidant shift.

The effect of topical latanoprost on corneal clarity; 1-year prospective study†

Purpose: Quantitatively investigate the effects of topical latanoprost on the corneal optical density parameters by using Scheimpflug system.Materials and methods: New cases of primary open-angle glaucoma treated with topical latanoprost as first-line treatment were enrolled in this prospective study. Corneal densitometry measurements obtained with the Scheimpflug system (Pentacam; Oculus, HR) at baseline and 1st, 3rd, 12th months after topical latanoprost treatment. For densitometry analysis, the 12-mm diameter area of the cornea was subdivided into 4 concentric radial zones and also into anterior, central, and posterior layers based on corneal depth. Pre and post-treatment values were compared statistically by a paired sample t-test.Results: The mean age of 18 female (66.7%) and 9 male (33.3%), totally 27 cases were 59.48 ± 10.1 years. There was no statistically significant difference between pretreatment and 1st-month post-treatment corneal densitometry values in all regions (p > 0.05 for all). Corneal densitometry values began to decline at 3rd month after treatment. The decrease continued until the 12th month of the beginning of the treatment and was significant in all zones except 2–6 mm of the anterior and central zones (p = 0.23, p = 0.08, respectively).Conclusion: Long-term administration of topical latanoprost may cause decrease in corneal densitometry measurements. Further prospective studies with a longer follow-up period are required to clarify the relationship between prostaglandin analogues and their effects on the cornea transparency.

Comprehensive sequencing of the myocilin gene in a selected cohort of severe primary open-angle glaucoma patients

Primary open-angle glaucoma (POAG) is the most common form of glaucoma, prevalent in approximately 1–2% of Caucasians in the UK over the age of 40. It is characterised by an open anterior chamber angle, raised intraocular pressure (IOP) and optic nerve damage leading to loss of sight. The myocilin gene (MYOC) is the most common glaucoma-causing gene, accounting for ~2% of British POAG cases. 358 patients were selected for next generation sequencing (NGS) with the following selection criteria: Caucasian ethnicity, intraocular pressure (IOP) 21–40 mm Hg, cup:disc ratio ≥0.6 and visual field mean deviation ≤−3. The entire MYOC gene (17,321 bp) was captured including the promoter, introns, UTRs and coding exons. We identify 12 exonic variants (one stop-gain, five missense and six synonymous variants), two promoter variants, 133 intronic variants, two 3′ UTR variants and 23 intergenic variants. Four known or predicted pathogenic exonic variants (p.R126W, p.K216K, p.Q368* and p.T419A) were identified across 11 patients, which accounts for 3.07% of this POAG cohort. This is the first time that the entire region of MYOC has been sequenced and variants reported for a cohort of POAG patients.

Microvascular endothelial function and primary open angle glaucoma.

Purpose:To determine the role of microvascular endothelial dysfunction as risk factor for primary open angle glaucoma.Methods:A cross-sectional study was conducted involving 114 Malay patients with POAG seen at the eye clinic of Hospital Universiti Sains Malaysia. Patients aged between 40 and 80 years who were diagnosed with other types of glaucoma, previous glaucoma filtering surgery or other surgeries except uncomplicated cataract surgery and pterygium surgery were excluded. A total of 101 patients who were followed up for dry eyes, age-related cataracts or post cataracts extraction surgery were recruited as control subjects. Those with family history of glaucoma or glaucoma suspect were excluded. Microvascular endothelial function was assessed using laser Doppler fluximetry and the process of iontophoresis. Iontophoresis with acetylcholine (ACh) and sodium nitroprusside (SNP) was used to measure microvascular endothelium-dependent and endothelium-independent vasodilatations, respectively.Results:In general, POAG patients demonstrated lower ACh% and AChmax values compared with controls. There was significant difference in microvascular endothelial function [ACh%: mean, 95% confidence interval = 503.1 (378.0, 628.3), and AChmax: mean, 95% confidence interval = 36.8 (30.2, 43.5)] between primary open angle glaucoma cases (p < 0.001) and controls [ACh%: mean, 95% confidence interval = 1378.4 (1245.4, 1511.3), and AChmax: mean, 95% confidence interval = 79.2 (72.1, 86.2)]; this difference remained significant even after controlling for potential confounders. Similar difference was also found in SNP% and SNPmax between POAG and controls (p < 0.001). Age and diastolic blood pressure were inversely correlated with microvascular endothelial function.Conclusion:There was an impairment of microvascular endothelial function and endothelial-independent vasodilatation in POAG patients. Microvascular endothelial function is a potential risk factor for POAG.

Screening of CYP1B1 Arg368His as predominant mutation in North Indian primary open angle glaucoma and juvenile onset glaucoma patients.

In India, mutations in Cytochrome P450 (CYP1B1) are a predominant cause of not only primary congenital glaucoma (PCG) but also involved in primary open angle glaucoma (POAG) and juvenile onset glaucoma (JOAG). After ethical clearance, 100 POAG patients, 30 primary angle closure glaucoma (PACG) patients and 130 ethnically matched controls were recruited in this study. Genomic DNA was isolated from the blood and screened for p.Arg368His mutation in CYP1B1 by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). On PCR-RFLP, 10/100 cases (10%) were found positive for Arg368His mutation. In North Indian POAG cases studied, p.Arg368His mutation was found only in heterozygous state. The frequency of p.Arg368His CYP1B1 mutation in heterozygote state (10.0%) observed in our study in North Indian POAG patients is the highest in comparison to frequency observed in other ethnic groups from Southern and Eastern India.

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

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.