Primary Open-angle Glaucoma Cases Research Articles

Genetic association of -1562C>T polymorphism in the MMP9 gene with primary glaucoma in a north Indian population

MMP (Matrix metalloproteinase) 9 is reported to affect glaucoma pathogenesis by altering intraocular pressure (IOP) through its role in remodeling the extracellular matrix (ECM) in the trabecular meshwork. A genetic variant at the promoter region in the MMP9 gene (-1562C>T) has a putative role in regulating its transcription rate and hence can affect genetic predisposition to primary glaucoma. The present study examined the association of -1562C>T promoter polymorphism in the MMP9 gene with Primary Open Angle Glaucoma (POAG) and Primary Angle Closure Glaucoma (PACG) in a north Indian population. A total of 729 subjects (POAG = 224, PACG = 138 and 367 controls) were recruited for the study. Genotyping for the promoter sequence variant was done with PCR-RFLP method. Genotypic and allelic frequency distribution of the POAG and PACG data sets were compared to that of controls by chi-square test and genetic association was tested under different genetic models as implemented under PLINK. Statistically significant difference was observed in the genotype frequencies between PACG cases and controls (p = 0.030). However, in the POAG cases, this difference was only borderline (p = 0.052). Genetic model analysis, under the dominant model revealed 1.6 and 1.4 fold increased susceptibility to PACG and POAG (p = 0.012, p = 0.032) respectively. A higher frequency of CT genotype was observed in PACG as well as POAG males as compared to female subjects. According to the dominant model, CT+TT genotype conferred 1.8 fold higher risk of developing PACG among male patients as compared to the control group (p = 0.048, OR = 1.87;1.00–3.50). Current findings suggest significant association of MMP9 -1562C>T polymorphism with primary glaucoma in the targeted north Indian population and warrant further replication of the findings in other populations.

Systemic Medication Associations with Presumed Advanced or Uncontrolled Primary Open-Angle Glaucoma

To identify associations between systemic medications and primary open-angle glaucoma (POAG) requiring a procedure using United States insurance claims data in a hypothesis-generating study. Database study. In total, 6130 POAG cases (defined as patients with POAG undergoing a glaucoma procedure) were matched to 30 650 controls (defined as patients undergoing cataract surgery but without a coded glaucoma diagnosis, procedure, or medication) by age, gender, and region of residence. Participant prescription drug use was calculated for the 5-year period before the glaucoma procedure or cataract surgery. Separately for individual generic drugs and drug classes, logistic regression was used to assess the association with POAG status. This was done across all generic drugs and drug classes that were prescribed in at least 1% of cases and controls. Analyses were adjusted for age, sex, region of residence, employment status, insurance plan type, and the total number of drugs prescribed. Odds ratio (OR) and 95% confidence intervals (CIs) for the association between each drug or drug class and POAG. The median age of participants was 72 years, and 52% were women. We tested for associations of POAG with 423 drug classes and 1763 generic drugs, resulting in a total of 2186 statistical tests and a Bonferroni-adjusted significance threshold of P < 2.3× 10-5. Selective serotonin reuptake inhibitors (SSRIs) were strongly associated with a reduced risk of POAG (OR, 0.70; 95% CI, 0.64-0.76; P= 1.0× 10-15); the most significant drug in this class was citalopram (OR, 0.66; 95% CI, 0.57-0.77; P= 1.2× 10-7). Calcium channel blockers were strongly associated with an increased risk of POAG (OR, 1.26; 95% CI, 1.18-1.35; P=1.8× 10-11); the most significant drug in this class was amlodipine (OR, 1.27; 95% CI, 1.18-1.37; P=5.9× 10-10). We present data documenting potential associations of SSRIs and calcium channel blockers with POAG requiring a procedure. Further research may be indicated to better evaluate any associates of serotonin metabolism or calcium channels in glaucoma, or establish whether the associations are due to variations in the patterns for prescribing these drugs.

The effect of trabeculectomy on serum brain-derived neurotrophic factor levels in primary open-angle glaucoma.

We aimed to investigate the effect of trabeculectomy on serum brain-derived neurotrophic factor (BDNF) levels. Our secondary goal was to compare serum and aqueous humor (AH) BDNF levels in primary open-angle glaucoma (POAG) and control subjects. This prospective, cross-sectional study consists of 20 eyes of with advanced-stage POAG who had trabeculectomy and 19 eyes of age- and sex-matched control healthy subjects who had cataract surgery. Serum and AH samples were obtained preoperatively in trabeculectomy group and control subjects. Serum samples were obtained at the third postoperative month in both groups. The aqueous humor and serum levels of BDNF at the surgery day were found to be strongly positive correlated (r = 0.868; p < 0.001). Serum and AH BDNF levels of POAG cases were significantly lower than control subjects at the surgery day (respectively p = 0.038, p = 0.011). In POAG cases, serum BDNF levels significantly increased at the third month after trabeculectomy while there was not a significant difference in control subjects with cataract surgery (p < 0.001; p = 0.717 respectively). Trabeculectomy was found to have a positive effect on serum BDNF levels in POAG cases.

Inter-relationship between ocular perfusion pressure, blood pressure, intraocular pressure profiles and primary open-angle glaucoma: the Singapore Epidemiology of Eye Diseases study

ObjectiveTo elucidate the inter-relationship between ocular perfusion pressure (OPP), blood pressure (BP), intraocular pressure (IOP) profiles and primary open-angle glaucoma (POAG) in a multiethnic Asian population.MethodsParticipants were recruited from the...

Correlation Between VEP Latency, CDR and PSD On Standard Automated Perimetry In Newly Diagnosed POAG Cases

Aim and Objective:- The current study was conducted to find out the correlation between Pattern reversal VEP (visual evoked potential) parameters, standard automated perimeter parameters and cup disc ratio (CDR) in newly diagnosed cases of POAG (primary open angle glaucoma).

Genetic analysis of Japanese primary open-angle glaucoma patients and clinical characterization of risk alleles near CDKN2B-AS1, SIX6 and GAS7.

PurposeTo test the genetic association between Japanese patients with primary open-angle glaucoma (POAG) and the previously reported POAG susceptibility loci and to perform genotype–phenotype analysis.MethodsGenetic associations for 27 SNPs from 16 loci previously linked to POAG were assessed using genome-wide SNP data of the primary cohort (565 Japanese POAG patients and 1,104 controls). Reproducibility of the assessment was tested in 607 POAG cases and 455 controls (second cohort) with a targeted genotyping approach. For POAG-associated variants, a genotype–phenotype correlation study (additive, dominant, recessive model) was performed using the objective clinical data derived from 598 eyes of 598 POAG patients.ResultsAmong 27 SNPs from 16 loci previously linked to POAG, genotypes for total of 20 SNPs in 13 loci were available for targeted association study. Among 8 SNPs in 3 loci that showed at least nominal association (P < 5.00E-02) in the primary cohort, a representative SNP for each loci (rs2157719 for CDKN2B-AS1, rs33912345 for SIX6, and rs9913911 for GAS7) were selected. For these SNPs the association was found significant in both the second cohort analysis and meta-analysis. The genotype–phenotype analysis revealed significant correlations between CDKN2B-AS1 (rs2157719) and decreased intraocular pressure (β = -6.89 mmHg, P = 1.70E-04; dominant model) after multiple corrections. In addition, nominal correlation was observed between CDKN2B-AS1 (rs2157719) and optic nerve head blood flow (β = -0.54 and -0.67 arbitrary units (AU), P = 2.00E-02 and 1.39E-02), between SIX6 (rs33912345) and decreased total peripapillary retinal nerve fiber layer thickness (β = -2.16 and -2.82 μm, P = 4.68E-02 and 2.40E-02, additive and recessive model, respectively) and increased optic nerve head blood flow (β = 0.44 AU, P = 2.20E-02; additive model) and between GAS7 (rs9913911) and increased cup volume (β = 0.03 mm3, P = 4.60E-02) and mean cup depth (β = 0.03 mm3, P = 4.11E-02; additive model) and decreased pattern standard deviation (β = -0.87 dB, P = 2.44E-02; dominant model).ConclusionThe association between SNPs near GAS7 and POAG was found in Japanese patients for the first time. Clinical characterization of the risk variants is an important step toward understanding the pathology of the disease and optimizing treatment of patients with POAG.

National and subnational prevalence and burden of glaucoma in China: A systematic analysis

BackgroundGlaucoma, the second leading cause of blindness, affects approximately 64.3 million individuals worldwide. In China, demographic ageing is in rapid progress. Yet detailed and up–to–date estimates of the scale of glaucoma are rare. We aimed to quantify and understand the prevalence and burden of glaucoma in China from 1990 to 2015, with projections until 2050.MethodsFor this systematic review and meta–analysis, we searched China National Knowledge Infrastructure (CNKI), Wanfang, Chinese Biomedicine Literature Database (CBM–SinoMed), PubMed, Embase and Medline using comprehensive search strategies to identify all relevant articles that have reported the prevalence of glaucoma in the general Chinese population. We used a multilevel mixed–effect meta–regression to estimate the prevalence rates of primary open–angle glaucoma (POAG) and primary angle–closure glaucoma (PACG), and a random–effects meta–analysis to pool the overall prevalence of secondary glaucoma. United Nations population data were used to estimate and project the number of people with glaucoma from 1990 to 2050. Univariable and multivariable meta–regressions were conducted to assess the association between the prevalence of POAG and PACG and relevant demographic and geographic factors. The national burden of POAG and PACG in the years 2000 and 2010 were distributed to six geographic regions accordingly.ResultsFrom 1990 to 2015, the prevalence of all glaucoma ranged from 2.59% (95% CI = 1.96–3.49) to 2.58% (95% CI = 1.94–3.47). For different subtypes of glaucoma, the overall prevalence of POAG ranged from 1.03% (95% CI = 0.67–1.58) in 1990 to 1.02% (95% CI = 0.67–1.57) in 2015, PACG from 1.41% (95% CI = 1.18–1.68) to 1.40% (95% CI = 1.17–1.68). The overall prevalence of secondary glaucoma was 0.15% (95% CI = 0.10–0.23) during this period. The number of people with all glaucoma in China was 5.92 million (95% CI = 4.47–7.97) in 1990, and 13.12 million (95% CI = 9.88–17.68) in 2015. This increasing trend was also witnessed in different subtypes of glaucoma. The number of people affected by POAG increased from 2.35 million (95% CI = 1.54–3.60) in 1990 to 5.22 million (95% CI = 3.40–7.98) in 2015, PACG from 3.22 million (95% CI = 2.70–3.84) to 7.14 million (95% CI = 5.97–8.53), and secondary glaucoma from 0.34 million (95% CI = 0.23–0.53) to 0.76 million (95% CI = 0.51–1.17). In 2015, more than half (54.42%) of the glaucoma cases were PACG, followed by POAG (39.79%) and secondary glaucoma (5.79%). By 2050, the number of all glaucoma cases in China will be 25.16 million (95% CI = 18.96–33.86). In the multivariable meta–regressions, the odds ratio (OR) for each decade’s increase in age was 1.43 (95% CI = 1.33–1.55) for POAG, and 1.65 (95% CI = 1.51–1.80) for PACG; males were more likely to have POAG (OR 1.36, 95% CI = 1.17–1.59), but less likely to have PACG (OR 0.53, 95% CI = 0.46–0.60) compared with females. After adjustment of age and gender, people living in urban areas were more likely to have POAG compared with those in rural areas (OR 1.54, 95% CI = 1.02–2.35). People in Northeast China were at a higher risk (OR 1.77, 95% CI = 1.07–2.94) of having PACG than people in East China. Among the six regions, East China owed the most POAG and PACG cases, whereas Northwest China owed the least.ConclusionsThis systematic review and meta–analysis suggests a substantial burden of glaucoma in China, with great variances among the different age groups, genders, settings and geographic regions. With the dramatic ageing trend in the next three decades, the prevalence and burden of glaucoma will continue to increase. More elaborate epidemiological studies are needed to optimise public health strategies for mitigating this important health problem.

Polymorphism rs10483727 in the SIX1/SIX6 Gene Locus Is a Risk Factor for Primary Open Angle Glaucoma in a Saudi Cohort.

Variant rs10483727 in the SIX1/SIX6 locus has been significantly associated with primary open angle glaucoma (POAG) in multiple ethnic groups. We conducted a case-control study to investigate the association between this variant and POAG in a Saudi cohort. Polymorphism rs10483727 was genotyped by using a TaqMan® assay in 186 subjects comprising 92 unrelated POAG cases and 94 controls all of Saudi origin. The "C" allele frequency was 0.33 and 0.45 among POAG cases and controls, respectively (odds ratio [OR] = 0.58, 95% confidence interval [CI] = 0.38-0.89; p = 0.013), suggesting a protective effect; and the "T" allele was associated with increased susceptibility to POAG (OR = 1.7, 95% CI = 1.11-2.58; p = 0.013). Genotype distribution was also significantly associated with POAG (χ2 = 6.41, df = 2, p = 0.041). Endophenotype traits such as intraocular pressure and cup/disk ratio did not show any significant genotype distribution in POAG cases. A binary logistic regression analysis used to evaluate the effects of age, gender, and genotype on the likelihood of having POAG showed that genotype distribution (p = 0.012) significantly affected the disease outcome as compared with age (p = 0.055) and sex (p = 0.432). The "T" allele of the rs10483727 polymorphism is an independent significant risk factor for POAG in the Saudi population.

A Multi-Locus Genetic Risk Score for Primary Open-Angle Glaucoma (POAG) Variants Is Associated with POAG Risk in a Mediterranean Population: Inverse Correlations with Plasma Vitamin C and E Concentrations.

Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide. The genetics of POAG are complex, and population-specific effects have been reported. Although many polymorphisms associated with POAG risk have been reported, few studies have analyzed their additive effects. We investigated, in a southern European Mediterranean population, the association between relevant POAG polymorphisms, identified by initial genome-wide association studies (GWASs) and POAG risk, both separately and as an aggregated multi-locus genetic risk score (GRS). Also, bearing in mind that oxidative stress is a factor increasingly recognized in the pathogenesis of POAG, we analyzed the potential association of the GRS with plasma concentrations of antioxidant vitamins (C and E). We carried out a case–control study including 391 POAG cases and 383 healthy controls, and analyzed four genetic polymorphisms (rs4656461-TMCO1, rs4236601-CAV1/CAV2, rs2157719-CDKN2B-AS1 and rs3088440-CDKN2A). An unweighted GRS including the four non-linked polymorphisms was constructed. A strong association between the GRS and POAG risk was found. When three categories of the GRS were considered, subjects in the top category of the GRS were 2.92 (95% confidence interval (CI): 1.79–4.77) times more likely to have POAG compared with participants in the bottom category (p < 0.001). Moreover, the GRS was inversely correlated with plasma vitamin C (p = 0.002) and vitamin E (p = 0.001) concentrations, even after additional adjustment for POAG status. In conclusion, we have found a strong association between the GRS and POAG risk in this Mediterranean population. While the additional correlation found between GRS and low levels of vitamins C and E does not indicated a causal relationship, it does suggest the need for new and deeper research into the effects of oxidative stress as a potential mechanism for those associations.

Polymorphism rs11656696 in GAS7 Is Not Associated with Primary Open Angle Glaucoma in a Saudi Cohort.

To conduct a case-control study to investigate the association between the polymorphism rs11656696 located in the growth arrest-specific 7 gene (GAS7)on human chromosome 17p13.1 and primary open angle glaucoma (POAG). The polymorphism rs11656696 was genotyped using the TaqMan® assay in 187 subjects comprising 92 unrelated POAG cases and 95 controls of Saudi Arabian origin. Association analysis between cases and controls revealed no significant genotype distribution under additive (p = 0.225), dominant (p = 0.635), or recessive (p = 0.085) models. Moreover, the allele frequency distribution was also nonsignificant (p = 0.70). The minor "A" allele frequency was 0.35 and 0.41 among POAG cases and controls, respectively. In addition, specific clinical indices used to assess severity of glaucoma such as intraocular pressure (IOP), cup/disk ratio, and number of antiglaucoma medications also did not show any significant genotype distribution in POAG cases. Moreover, a binary logistic regression analysis did not show any significant effect of age, sex, or genotype on disease outcome. Polymorphism rs11656696 is not associated with POAG nor any of its endophenotypic traits such as IOP and cup/disk ratio and is thus not a risk factor for POAG in this Saudi cohort.

CRISPR-Cas9–based treatment of myocilin-associated glaucoma

Primary open-angle glaucoma (POAG) is a leading cause of irreversible vision loss worldwide, with elevated intraocular pressure (IOP) a major risk factor. Myocilin (MYOC) dominant gain-of-function mutations have been reported in ∼4% of POAG cases. MYOC mutations result in protein misfolding, leading to endoplasmic reticulum (ER) stress in the trabecular meshwork (TM), the tissue that regulates IOP. We use CRISPR-Cas9-mediated genome editing in cultured human TM cells and in a MYOC mouse model of POAG to knock down expression of mutant MYOC, resulting in relief of ER stress. In vivo genome editing results in lower IOP and prevents further glaucomatous damage. Importantly, using an ex vivo human organ culture system, we demonstrate the feasibility of human genome editing in the eye for this important disease.

Visual Evoked Potentials in Primary Open Angle Glaucoma.

Background and Aims Visual evoked potentials (VEPs) assess the integrity of the visual pathways from the optic nerve to the occipital cortex. Optic disc cupping and visual field loss have been associated with prolongation of latency of VEP in primary open angle glaucoma (POAG). Methods Pattern reversal and flash VEP tests were done in consenting 20 primary open angle glaucoma eyes and 40 normal control eyes. Results In POAG cases, the refractive error [3.51 ± 1.88 versus 1.88 ± 1.11, D, p = 0.001], cup-disc ratio in percent [66.00 ± 16.98 versus 28.50 ± 5.80, p = 0.001], intraocular pressure [19.55 ± 2.08 versus 11.65 ± 1.64, mmHg, p = 0.001], and automated visual field pattern standard deviation [4.13 ± 6.96 versus 1.64 ± 0.45, dB, p = 0.001] were significantly more than in control. The visual acuity [0.41 ± 0.29 versus 1.00 ± 0.00, p = 0.001], foveal visual sensitivity [25.92 ± 6.88 versus 33.48 ± 1.75, dB, p = 0.001], and automated visual field mean deviation [−9.63 ± 10.58 versus 0.07 ± 1.54, dB, p = 0.001] were significantly less in cases than in control. Among VEP variables, pattern reversal latency N145 [149.00 ± 15.75 versus 137.52 ± 15.20, ms, p = 0.011], flash amplitude N75 [2.18 ± .57 versus 1.47 ± .38, μV, p = 0.001], and flash amplitude N145 [1.99 ± .39 versus 1.43 ± .38, μV, p = 0.001] were increased in cases. The pattern reversal amplitude N75 [1.97 ± .35 versus 2.47 ± .58, μV, p = 0.001], amplitude P100 [3.09 ± .46 versus 6.07 ± 1.44, μV, p = 0.001], and amplitude N145 [2.21 ± .58 versus 4.45 ± 1.99, μV, p = 0.001] were decreased in cases. Conclusions POAG caused glaucomatous damage to optic pathway.

Variants in the PRPF8 Gene are Associated with Glaucoma

Glaucoma is the cause of irreversible blindness worldwide. Mutations in six genes have been associated with juvenile- and adult-onset familial primary open angle glaucoma (POAG) prior to this report but they explain only a small proportion of the genetic load. The aim of the study is to identify the novel genetic cause of the POAG in the families with adult-onset glaucoma. Whole exome sequencing (WES) was performed on DNA of two affected individuals, and predicted pathogenic variants were evaluated for segregation in four affected and three unaffected Dutch family members by Sanger sequencing. We identified a pathogenic variant (p.Val956Gly) in the PRPF8 gene, which segregates with the disease in Dutch family. Targeted Sanger sequencing of PRPF8 in a panel of 40 POAG families (18 Pakistani and 22 Dutch) revealed two additional nonsynonymous variants (p.Pro13Leu and p.Met25Thr), which segregate with the disease in two other Pakistani families. Both variants were then analyzed in a case-control cohort consisting of Pakistani 320 POAG cases and 250 matched controls. The p.Pro13Leu and p.Met25Thr variants were identified in 14 and 20 cases, respectively, while they were not detected in controls (p values 0.0004 and 0.0001, respectively). Previously, PRPF8 mutations have been associated with autosomal dominant retinitis pigmentosa (RP). The PRPF8 variants associated with POAG are located at the N-terminus, while all RP-associated mutations cluster at the C-terminus, dictating a clear genotype-phenotype correlation.

Accuracy of isolated-check visual evoked potential technique for diagnosing primary open-angle glaucoma.

The aim of this study was to determine the diagnostic accuracy, sensitivity and specificity of isolated-check visual evoked potentials (icVEP) in primary open-angle glaucoma (POAG). Ninety POAG patients and sixty-six healthy controls were recruited consecutively. All subjects underwent icVEP and visual field testing. Swept icVEP response functions were obtained by increasing contrast in six stimulus steps, recording the electroencephalogram synchronized to the stimulus display's frame rate and calculating the corresponding signal-to-noise ratio (SNR) of the response at the fundamental frequency to evaluate visual function. Depth of modulation of the check luminance was increased as follows: 2, 4, 8, 14, 22 and 32%, about an equal level of standing contrast, so that the pattern appeared and disappeared at a frequency of 10.0Hz. SNR above 0.85 was deemed to be significant at the 0.1 level and SNR above 1 significant at the 0.05 level. The results show that SNR is contrast dependent. It significantly rose as contrast increased. The areas under receiver-operating-characteristic curves (AUCs) indicating classification accuracy for all POAG cases in comparison with normal subjects were 0.790 (sensitivity 91.1%, specificity 69.7%) with the cutoff SNR of 0.85, and 0.706 (sensitivity 95.6%, specificity 51.5%) with the cutoff SNR of 1. The AUC of early glaucoma cases (EG) in comparison with normal subjects was 0.801 (sensitivity 93.3%, specificity 69.7%) with the cutoff SNR of 0.85, and 0.717 (sensitivity 97.8%, specificity 51.5%) with the cutoff SNR of 1. icVEP has good diagnostic accuracy (high sensitivity and moderate specificity) in distinguishing early POAG patients from healthy subjects. It might be a promising device to use in conjunction with complementary functional and structural measures for early POAG detection.

Polymorphism rs547984 on human chromosome 1q43 is not associated with primary open angle glaucoma in a Saudi cohort

BackgroundTo investigate the association between polymorphism rs547984, located in close proximity to the Zona Pellucida Glycoprotein 4 (ZP4) gene on human chromosome 1q43 and primary open angle glaucoma (POAG).MethodPolymorphism rs547984 was genotyped using Taq-Man® assay in 185 subjects comprising of 90 unrelated POAG cases and 95 controls of Saudi origin.ResultsAssociation analysis between cases and controls revealed no significant genotype distribution under additive (p = 0.356), dominant (p = 0.517) and recessive (p = 0.309) models. Besides, the allele frequency distribution was also found to be non-significant (p = 0.70). The minor “A” allele frequency was found to be 0.49 and 0.50 among POAG cases and controls, respectively. In addition, specific clinical indices used to assess severity of glaucoma such as intraocular pressure (IOP), cup/disc ratio and number of anti-glaucoma medication also did not show any significant genotype distribution in POAG cases.ConclusionPolymorphism rs547984 is neither associated with any clinical indices important for POAG such as IOP and cup/disc ratio nor is a risk factor for POAG in the Saudi cohort.

A Histologic Categorization of Aqueous Outflow Routes in Familial Open-Angle Glaucoma and Associations With Mutations in the MYOC Gene in Japanese Patients.

This study evaluated specific relationships between pathogenic mechanisms and genetic polymorphisms in primary open-angle glaucoma (POAG). We analyzed the morphologies of trabeculectomy specimens obtained from patients with familial POAG. We used light microscopy and transmission electron microscopy to examine specimens obtained from 17 eyes of 14 patients with familial POAG. We also conducted exome analyses of two families and used targeted Sanger sequencing to analyze samples obtained from the remaining patients. The POAG cases examined in this study were divided into two groups based on morphologic characteristics. Group A eyes (7 eyes from 5 patients) had an abnormally thick trabecular meshwork (TM), whereas group B eyes (10 eyes from 9 patients) had a TM of normal thickness. The characteristics of the outflow routes in group A eyes were remarkable and included apoptotic TM cells, abnormally thickened TM basement membranes, fused TM beams, and occluded Schlemm's canals. All group A patients harbored mutations (F369L, P370L, T377M, and T448P) in the myocilin (MYOC) gene that were not found in group B patients. Although age matching of morphologic changes in the outflow routes was impossible due to the small sample size, this study suggests that abnormal TM cells may cause sequential damage in abnormally thickened TM basement membranes, TM cell apoptosis, TM beam fusion, and the occlusion of Schlemm's canals. The four detected MYOC mutations appeared to be associated with morphologic changes in the TM and the underlying pathogenesis of a subtype of familial POAG.

A comparative study of benzalkonium chloride-free latanoprost versus benzalkonium chloride-preserved latanoprost on ocular surface health in patients of primary open angle glaucoma

Background: Prolonged use of anti-glaucoma therapy leads to development of ocular surface disease (OSD). The purpose of this study was to compare the effect of Benzalkonium chloride (BKC)-free latanoprost and Benzalkonium chloride (BKC)-preserved latanoprost on ocular surface health in patients of primary open angle glaucoma (POAG).Methods: This was a prospective, open-label, randomized, interventional, switch trial. 30 established cases of POAG who were already on BKC-preserved latanoprost for atleast more than three months were enrolled. Their Schirmer test and Tear film break-up time (TBUT) were recorded at the baseline. They were required to answer an ocular surface disease index (OSDI) questionnaire from which an OSDI score was calculated. They were switched to BKC-free latanoprost for another three months. On their follow-up visit at 6 weeks and 12 weeks, Schirmer test and Tear film break up time were performed again and OSDI score was calculated.Results: Schirmer test increased from 6.73±3.77 mm at baseline to 9.53±3.67 mm at 6 weeks and 11.97±3.53 mm at 12 weeks (p=0.001). Mean TBUT improved significantly from 6.77±3.82 seconds at baseline to 8.63±3.91 seconds at 6 weeks to 10.47±3.76 seconds at 12 weeks (p=0.001). OSDI score decreased from 31.55±23.32 at baseline to 23.42±21.93 at 6 weeks to 15.82±20.10 at 12 weeks (p=0.001).Conclusions: BKC-free latanoprost led to improvement in tear film status or ocular surface health of glaucoma patients as compared to BKC-preserved latanoprost.

A Pilot Study to Evaluate the Oral Microbiome and Dental Health in Primary Open-Angle Glaucoma.

To evaluate possible associations between primary open-angle glaucoma (POAG), dental health, and the oral microbiome. Case-control study was conducted at SUNY Downstate. Adult subjects (40 to 87 y) were recruited as POAG cases (n=119) and controls without glaucoma (n=78) based on visual field and optic nerve criteria. Overall 74.6% were African Americans (AA). Information on medical history and oral health was collected and ophthalmologic examinations were performed. Mouthwash specimens (28 AA cases and 17 controls) were analyzed for bacterial DNA amounts. Analyses were limited to AAs as the predominant racial group. Outcome measures included number of natural teeth, self-reported periodontal health parameters, and amounts and prevalence of oral bacterial species. Logistic regression was used to evaluate associated factors and potential interactions. Cases and controls had similar age (mean: 62.2 and 60.9 y, respectively, P>0.48), and frequency of hypertension, diabetes, but cases had a higher proportion of men (P<0.04). On average (±SD), cases had fewer natural teeth than controls [18.0 (±11.1) vs. 20.7 (±9.4)]. Having more natural teeth was inversely associated with POAG, in multivariable analyses, at older ages [eg, odds ratio (95% confidence interval) at age 55: 1.0 (0.95-1.06), P=0.98 vs. at age 85: 0.87 (0.79-0.96), P=0.007]. Amounts of Streptococci were higher in cases than controls (P<0.03) in samples from the subset of subjects analyzed. The number of teeth (an oral health indicator) and alterations in the amounts of oral bacteria may be associated with glaucoma pathology. Further investigation of the association between dental health and glaucoma is warranted.

Contribution of Mutations in Known Mendelian Glaucoma Genes to Advanced Early-Onset Primary Open-Angle Glaucoma.

Primary open-angle glaucoma (POAG) and primary congenital glaucoma (PCG) with Mendelian inheritance are caused by mutations in at least nine genes. Utilizing whole-exome sequencing, we examined the disease burden accounted for by these known Mendelian glaucoma genes in a cohort of individuals with advanced early-onset POAG. The cases exhibited advanced POAG with young age of diagnosis. Cases and examined local controls were subjected to whole-exome sequencing. Nine hundred ninety-three previously sequenced exomes of Australian controls were called jointly with our dataset. Qualifying variants were selected based on predicted pathogenicity and rarity in public domain gene variant databases. Case-control mutational burdens were calculated for glaucoma-linked genes. Two hundred eighteen unrelated POAG participants and 103 nonglaucomatous controls were included in addition to 993 unexamined controls. Fifty-eight participants (26.6%) harbored rare potentially pathogenic variants in known glaucoma genes. Enrichment of qualifying variants toward glaucoma was present in all genes except WDR36, in which controls harbored more variants, and TBK1, in which no qualifying variants were detected in cases or controls. After multiple testing correction, only MYOC showed statistically significant enrichment of qualifying variants (odds ratio [OR] = 16.62, P = 6.31×10-16). Rare, potentially disease-causing variants in Mendelian POAG genes that showed enrichment in our dataset were found in 22.9% of advanced early-onset POAG cases. MYOC variants represented the largest monogenic cause in POAG. The association between WDR36 and POAG was not supported, and the majority of POAG cases did not harbor a potentially disease-causing variant in the remaining Mendelian genes.

Lack of association between polymorphism rs540782 and primary open angle glaucoma in Saudi patients

BackgroundTo investigate whether polymorphism rs540782 on chromsome 1, in close proximity to the Zona Pellucida Glycoprotein 4 (ZP4) gene, is a risk factor for primary open angle glaucoma (POAG).MethodThe study genotyped 92 unrelated POAG cases and 95 control subjects from Saudi Arabia using Taq-Man® assay.ResultsThe genotype frequency distribution did not deviate significantly from the Hardy-Weinberg equilibrium (p > 0.05). Overall, both the genotype and allele frequencies were not significantly different between cases and controls. The minor ‘C’ allele frequency was 49.4%, which was comparable to the Japanese population and higher than the Indian and Afro-Caribbean populations. Similarly, no significant association was found between genotypes and systemic diseases and health awareness/behavior domain variables. Importantly, glaucoma specific indices, such as intraocular pressure, cup/disc ratio and number of anti-glaucoma medication, also showed no statistically significant effect of genotypes within POAG cases.ConclusionPolymorphism rs540782 is not a risk factor for POAG in the Saudi cohort.