Primary Angle Closure Glaucoma Cases Research Articles

Proportion of Angle Closure Glaucoma in Tamale, Ghana.

In the largest clinic-based study to date, our review of 588 patients presenting with glaucoma in Northern Ghana revealed 36% of these had primary angle closure glaucoma. Glaucoma is the second leading cause of blindness worldwide. In Africa, glaucoma is an established public health problem, and primary angle-closure glaucoma (PACG) is not commonly discussed. Recognizing it is important because of its negative impact on visual morbidity, and also because its treatment is different from primary open angle glaucoma (POAG). In response to the observation of many PACG cases at the Northern Community Eye Hospital in Tamale, Ghana, we investigated the proportion of those attending with a first diagnosis of glaucoma who had PACG. Using the electronic records, we identified 976 patients who attended with a first diagnosis of glaucoma between January 2021 and October 2022. Of these, 588 met the inclusion criterion of a clear glaucoma subtype diagnosis. Of these 316 (53.7%) had POAG, 210 (35.7%) PACG, and 62 (10.5%) secondary glaucoma. Thus, over a third of presenting glaucomas had PACG. This study highlights that PACG is present in about a third of patients presenting to our clinic in North Ghana . Our study demonstrates the importance of a clear diagnostic pathway including gonioscopy in the assessment of glaucoma patients and the consideration of wider training on angle closure glaucoma diagnosis and management.

Interaction of background genetic risk, psychotropic medications, and primary angle closure glaucoma in the UK Biobank.

Background/AimsPsychotropic medications have been reported as a risk factor for angle closure disease. However, the interaction between background genetic risk for primary angle closure glaucoma (PACG) and susceptibility to angle closure disease among psychotropic medication users has not been investigated. Here we demonstrate the utility of a genome-wide polygenic risk score (PRS) in identifying and risk-stratifying subjects with PACG and investigate the association between PACG genetic burden and exposure to psychotropic medications on prevalent angle closure.MethodsThis analysis used the UK Biobank dataset, a prospective cohort study of 502,506 UK residents. We constructed a PACG PRS for participants using genome-wide association study summary statistics from a multiethnic meta-analysis using the Lassosum method.ResultsAmong the 441,054 participants, 959 (0.22%) were identified as PACG cases. Individuals with PACG had higher PRS compared to those without PACG (0.24±1.03 SD vs. 0.00±1.00 SD, p<0.001) and PACG prevalence increased with each decile of higher PRS. Among individuals using psychotropic medication, those with PACG had higher average PRS (0.31±1.00 SD vs. 0.00±1.00 SD, p<0.001) and were more likely to have a PRS in upper deciles of polygenic risk (p = 0.04). At each decile of PRS, psychotropic medication use was associated with increased risk of PACG. These effects were more pronounced and significant in higher deciles.ConclusionWe demonstrate the utility of a PRS for identifying individuals at higher risk of PACG. Additionally, we demonstrate an important relationship where the association between psychotropic medications use and PACG diagnosis varies across the polygenic risk spectrum.

Prevalence of Plateau Iris in Primary Angle Closure Glaucoma: An Egyptian Hospital Based Ultrasound Biomicroscopy Study.

PurposeTo determine the distribution and the anatomical characteristics of plateau iris (PI) in primary angle closure glaucoma (PACG) using ultrasound biomicroscopy (UBM).MethodsFifty UBM images of PACG cases were studied over one year by retrospective analysis. The data from UBM images including angle opening distance at 500 and 750 μm (AOD500 and AOD750), trabecular-iris angle (TIA), angle recess area at 750 μm (ARA750), maximum ciliary body thickness (CBTmax), anterior placement of ciliary processes (APCP), central anterior chamber depth (CACD), axial lens thickness (ALT), and ciliary sulcus status were analyzed and compared between the PI and non-PI cases.ResultsEighteen cases had PI (36%). The mean AOD500, AOD750, and TIA were significantly smaller in PI than in non-PI eyes (P = 0.01; P = 0.046; and P = 0.026). Values of the ARA750 and CBTmax were not significantly different between the two groups (P = 0.208 and P = 0.368). CACD was deeper in the PI group (P = 0.011). ALT was higher in the non-PI group (P = 0.001). The mean APCP of the PI group was more than those of the non-PI group (P < 0.001). The number of cases with obliterated ciliary sulcus in more than two quadrants was significantly more in the PI group (P < 0.001).ConclusionAround one-third of PACG eyes were found to have PI on UBM imaging. The number of obliterated ciliary sulcus and APCP were important UBM parameters that help in PI diagnosis.

Racial and Sociodemographic Disparities in the Detection of Narrow Angles before Detection of Primary Angle-Closure Glaucoma in the United States

To assess the proportion of newly diagnosed cases of primary angle-closure glaucoma (PACG) with and without prior diagnosis of anatomical narrow angle (ANA) and to identify sociodemographic risk factors for late detection (PACG without prior ANA diagnosis). Retrospective cohort study. One hundred two thousand six hundred seventeen patients with PACG were identified from the Optum Clinformatics Data Mart Database (2007-2019). Patients with newly diagnosed PACG met the following criteria: (1) diagnosis made by an ophthalmologist, (2) disease observable for at least 12 months before diagnosis, and (3) no history of treatment before diagnosis unless preceded by a diagnosis of ANA. Multivariate logistic regression modeling was performed to identify sociodemographic risk factors for late detection. Proportion of patients with newly diagnosed PACG without prior ANA diagnosis and sociodemographic factors associated with late detection. Thirty-one thousand forty-four patients were eligible. More than 70% of PACG cases were detected without prior ANA diagnosis, regardless of patient age, sex, or race. The odds of late detection were significantly higher (P < 0.001) among men (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.25-1.40), Black patients (OR, 1.25; 95% CI, 1.15-1.37), and patients 80 years of age or older (OR, 1.28; 95% CI, 1.11-1.47) or living in Southern (OR, 1.30; 95% CI, 1.22-1.40) or Pacific (OR, 1.27; 95% CI, 1.16-1.36) regions. Findings were similar for patients with PACG with a record of gonioscopy and treatment or with a 24-month lookback period. Most patients who receive a new diagnosis of PACG in the United States do not have a prior diagnosis of ANA. The elderly, men, and Black patients are at higher risk of late detection. A need exists for increased disease awareness among providers and more accessible tools to detect patients at risk of developing PACG.

Clinical implication of recent randomized control trial in primary angle-closure disease management.

Blindness due to primary angle-closure glaucoma (PACG) can be reduced significantly if the ongoing angle-closure process is arrested at an early stage. Various treatments such as laser peripheral iridotomy (LPI), iridoplasty, and clear lens extraction (CLE) have been advocated as first-line therapy for primary angle-closure (PAC), PACG, and high-risk cases of primary angle-closure suspect (PACS). EAGLE study, propagated the effectiveness of CLE over LPI for the management of primary angle closure and have sparked controversy regarding the role of LPI as a first line procedure. Randomized controlled trials (RCT), systematic reviews, and meta-analyses of RCTs done on the same question provide us with a solid base for creating guidelines/modules for our day-to-day clinical practice. A systematic review was conducted, searching several databases, including PubMed, Cochrane Library, EMBASE, and ClinicalTrials.gov, for the last 16 years (January 2005-December 2021) for RCTs with data published related to primary angle-closure disease (PACD). The search strategy included the following terms: "Primary Angle Closure disease," "Primary Angle Closure Glaucoma," "Primary Angle Closure," "Primary Angle Closure Suspect," "clear lens extraction," "laser iridotomy," "laser peripheral iridotomy," "argon laser peripheral iridoplasty," "selective laser trabeculoplasty," "trabeculectomy," "randomized control trial," and "meta-analysis of randomized control trial." In this review, we will discuss recently published RCTs (within the last 16 years) for the management of PACD and their clinical implications in day-to-day practice.

Association analysis of variants rs35934224 in TXNRD2 and rs6478746 in LMX1B in primary angle-closure and pseudoexfoliation glaucoma.

Previous genome-wide studies have demonstrated significant pathogenic association between variants rs35934224 within TXNRD2 and rs6478746 near LMX1B in primary open-angle glaucoma. We investigated the association between these variants in primary angle-closure glaucoma (PACG) and pseudoexfoliation glaucoma (PXG) patients of Saudi origin. In a case-control study, DNA samples from 249 controls (135 men and 114 women), 100 PACG cases (44 men and 56 women), and 95 PXG cases (61 men and 34 women) were genotyped by TaqMan® based real-time PCR. Statistical tests were performed to evaluate genetic association with glaucoma types and related clinical indices. The allele frequencies of rs35934224 and rs6478746 did not show significant variation in PACG and PXG than controls, except that the rs35934224[T] allele was found to be significantly low among PXG women (0.10) as compared to controls (0.21) (odds ratio = 0.38, 95% confidence interval = 0.16-0.94, p = 0.024). Rs35934224 genotypes showed a nominal-to-borderline protective association with PACG and PXG among women in different genetic models. However, except for the over-dominant model in PACG (p = 0.0095), none of the effects survived Bonferroni's correction (p < 0.01). Rs6478746 showed no significant genotype or allelic association with PACG and PXG. Regression analysis showed no influence on disease outcome, and neither showed any correlation with intraocular pressure and cup/disk ratio in both PACG and PXG. Variants rs35934224 in TXNRD2 and rs6478746 near LMX1B are not associated with PACG and PXG in the Saudi cohort, but rs35934224 may confer modest protection among women. Further population-based studies are needed to validate these results.

Suggestive evidence of genetic association of −572G > C polymorphism with primary open angle glaucoma in a North Indian Punjabi population

BackgroundIL6 is an important candidate gene implicated in the pathogenesis of glaucoma. The present study assessed the genetic association of −174G > C and −572G > C polymorphisms in the IL6 promoter region with primary open angle glaucoma (POAG) and primary angle closure glaucoma (PACG) in a north Indian Punjabi cohort. Methods910 subjects (313 POAG, 148 PACG cases and 449 controls) were recruited. Genotyping was done by TaqMan assays. Genetic association was tested under different genetic models using Plink. Diplotype and linkage disequilibrium (LD) analysis was done through Haploview. Association of clinical parameters with the genotypes was assessed by one-way ANOVA. Adjustment for potential confounding variables was done by binary logistic regression. IL6 levels were measured in POAG patients and controls. Results572G > C variant showed marginal difference in genotype frequency between pooled cases and POAG subgroup with respect to controls (p = 0.042; OR = 1.33; and p = 0.041; OR = 1.37). The GC genotype conferred 1.37-fold protection under codominant model in POAG cases (p = 0.034, OR = 1.37, 95% CI = 1.02–1.85; pcorr = 0.025, OR = 1.45, 95% CI = 1.04–2.02). The mean value for IOP was elevated among cases having ‘CC’ genotype at the −572G > C locus (p = 0.037).Lower levels of IL6 were detected in POAG patients in plasma samples (p = 0.0001). ConclusionThe study reports suggestive evidence for −572G > C variant in IL6 in affecting genetic susceptibility to POAG in the targeted North Indian Punjabi cohort. A correlation of IL6 levels in aqueous humor (AH) and systemic circulation in POAG was observed, the functional and diagnostic relevance of which may be further investigated.

Association of TGFB -509C>T promoter polymorphism with primary angle closure glaucoma in a North Indian Punjabi cohort

PurposeTransforming growth factor beta (TGFB) is an important candidate gene implicated in glaucoma pathogenesis because it affects retinal ganglionic cell survival. The present study assessed the genetic association of -509C > T variant in the TGFB promoter region with primary open angle glaucoma (POAG) and primary angle closure glaucoma (PACG) in a North Indian Punjabi population.MethodA total of 867 subjects (307 POAG, 133 PACG cases and 427 controls) were recruited from the targeted population. Genotyping was done by PCR-RFLP method and the data was analyzed using PLINK software (v1.07). Logistic regression under different genetic models was applied and genotype phenotype correlation was assessed by one-way ANOVA.ResultA statistically significant difference in the frequency of heterozygotes among PACG cases (53.16%) and controls (30.07%) (p = 0.0002) was observed. Genetic model analysis revealed that mutant “TT” genotype conferred 2-fold risk towards PACG development under recessive model (p = 0.0019) while dominant model and co-dominant model provided 0.62 and 0.37 fold protection against PACG (p = 0.025 and p = 0.0001, respectively). Data segregation based on sex revealed a strong protective effect of heterozygous ‘CT’ genotype against progression of PACG among females (p = 0.002, OR = 0.37, 95% CI = 0.19–0.70), but conferred 2.14-fold risk among female POAG subjects (p = 0.013).ConclusionThe study revealed a strong genetic association of -509C > T variant in TGFB with PACG in females. There is a need to replicate the results in a larger PACG cohort in other populations and further assess the contribution of sex specific factors in modifying genetic susceptibility to PACG.

Effect of intraoperative application of viscoelastic on corneal endothelium during trabeculectomy with mitomycin C surgery in primary angle-closure glaucoma patients

Background Mitomycin C (MMC), as a wound-healing modulatory factor, can be applied during trabeculectomy to increase its success rate. This may affect the morphology and function of corneal endothelium as well as its central cell count.Aim The aim of this study was to investigate the effect of intracameral injection of viscoelastic combined with subconjunctival application of viscoelastic in trabeculectomy with MMC performed for uncontrolled chronic primary angle-closure glaucoma (PACG) in order to decrease the MMC side effects on the corneal endothelial cells.Patients and methods This is a prospective randomized comparative case-series study that included 70 eyes of 70 patients with uncontrolled chronic PACG. The patients were referred for glaucoma surgery in a tertiary hospital. They were randomized into two groups with 35 eyes in each group: group 1 included 35 eyes that underwent subscleral trabeculectomy with MMC with intracameral injection of dispersive viscoelastic and subconjunctival application of cohesive viscoelastic, while group 2 included 35 eyes that underwent subscleral trabeculectomy with MMC application only. In both groups, endothelial cells were assessed by specular microscopy preoperatively and postoperatively. The outcome measures included the corneal endothelial cell density, hexagonality (HEX), coefficient of variation of cell size, central corneal thickness, as well as intraocular pressure (IOP).Results The mean age of the patients was 53.43±5.14 years in group 1 and 52.54±4.2 years in group 2. The IOP decreased from 31.09±3.17 mmHg preoperatively to 11.2±0.8, 11.8±0.9, 11.9±0.9, and 11.9±0.9 mmHg at 1, 3, 6, and 12 months postoperatively, respectively, in group 1, while it decreased from 30.5±3.7 mmHg preoperatively to 13.7±1.1, 14.4±0.9, 14.6±0.8, and 14.7±0.7 mmHg at 1, 3, 6, and 12 months postoperatively, respectively, in group 2. The corneal endothelial cell density significantly decreased from 2482±179 cells/mm2 preoperatively to 2350±62 cells/mm2 at 12 months postoperatively (P<0.001) in group 1, while it significantly decreased from 2461.17±41.58 cells/mm2 preoperatively to 2273±37.5 cells/mm2 at 12 months postoperatively (P<0.001) in group 2, with a significant difference between the two groups (P<0.001). The coefficient of variation as a measurement of polymegathism was significantly increased from 27.21±0.41 preoperatively to 27.73±0.478 postoperatively in group 1 (P<0.001), while it significantly increased from 27.18±0.40 preoperatively to 27.72±0.4 postoperatively in group 2 (P<0.001). HEX, which is an indication of variability in HEX shape, was significantly decreased from 71.5±0.4% preoperatively to 62.0±1.8% at 1 month and then significantly increased to 68.2±1.8% at 12 months postoperatively in group 1 (P<0.001). On the other hand, it decreased from 71.55±0.40% preoperatively to 62.0±1.75% at 1 month and then significantly increased to 68.17±1.77% at 12 months postoperatively in group 2 (P<0.001). Intracameral combined with subconjunctival application of viscoelastic significantly reduced the IOP in group 1 to 11.94±0.91 mmHg more than in group 2 (14.69±0.76 mm Hg) at the end of the follow-up period (P<0.001).Conclusion Intracameral injection of dispersive viscoelastic, in addition to subconjunctival injection of cohesive viscoelastic, may be a good method to preserve the corneal endothelium in PACG cases, for which trabeculectomy with MMC application was performed. Moreover, this extrastep may increase the trabeculectomy success rate and reduce its complications.

Role of matrix metalloproteinase-9 gene polymorphisms in glaucoma: A hospital-based study in Chinese patients.

BackgroundGlaucoma is the irreversible vision loss and contributes second leading cause of blindness worldwide. Matrix metalloproteinase‐9 (MMP‐9) is involved with remodeling and destruction of extracellular matrix. Elevated MMP‐9 levels and various functional variants of MMP‐9 have been associated with glaucoma in different population. In the current investigation, we tested association of MMP‐9 common variants with different clinical categories of glaucoma in Chinese population.Materials and MethodsWe enrolled total of 396 glaucoma patients those reported to hospital comprising of 212 primary angle closure glaucoma (PACG) cases and 184 primary open‐angle glaucoma POAG patients. In addition, 329 normal individuals from similar geographical areas were enrolled as healthy controls. Five common single nucleotide polymorphisms (rs3918242, rs3918254, rs2250889, rs3918249, and rs17576) were genotyped by PCR‐RFLP. Plasma levels of MMP‐9 were quantified by ELISA.ResultsHeterozygotes (GC) and allele “G” for rs2250889 polymorphism were more frequent in PACG cases compared with healthy controls (GC: P < .0001, OR = 2.26; G: P < .0001, OR = 1.19). Similarly, heterozygous mutant and minor allele for rs3918242 polymorphism were more prevalent in POAG in comparison with healthy controls. Interestingly, distribution of rs17576 variant was statistically higher in both PACG and POAG cases than healthy controls. Furthermore, analysis of plasma MMP‐9 with MMP‐9 polymorphisms revealed significant association of rs2250889, rs3918242, and rs17576 with plasma levels of the protein.ConclusionsMMP‐9 mutants are associated with elevated plasma MMP‐9 and predisposed to development of glaucoma.

Integration of Genetic and Biometric Risk Factors for Detection of Primary Angle Closure Glaucoma

The purpose of this study was to investigate whether the addition of primary angle closure glaucoma (PACG)-associated genetic loci allows improved detection of PACG, compared to anterior segment parameters measured by imaging. Case-control study. Genotype data of the 8 PACG single-nucleotide polymorphisms (SNPs) (rs11024102 at PLEKHA7, rs3753841 at COL11A1, rs1015213 located between PCMTD1 and ST18 on Chromosome 8q, rs3816415 at EPDR1, rs1258267 at CHAT, rs736893 at GLIS3, rs7494379 at FERMT2, and rs3739821 mapping in between DPM2 and FAM102A) were available. Customized software was used to measure anterior segment optical coherence tomography (ASOCT) parameters, namely, anterior chamber depth, width, and area (ACD, ACW, and ACA) and lens vault (LV). Statistical analysis for positive predictive values was modeled using the receiver operating characteristic curve (AUC). Statistical significance comparing predictive power of the different parameters was calculated using permutation. A total of 388 PACG subjects and 751 controls with both ASOCT and genetic data were available for analysis. Anterior segment parameters including ACD, ACA, and LV had excellent predictive value (AUCs >0.94), except ACW (AUC=0.65), for identifying PACG. The inclusion of genetic risk alleles (either singly or as a composite genetic risk score for 8 genomewide association study SNPs) to ACD only provided a+0.50% improvement in reclassifying PACG cases and controls over and above the discriminatory value of ACD. This+0.50% improvement was not statistically significant (P > .05). Although significant on their own, the incorporation of genetic data in the context of anterior segment imaging parameters like ACD provided only a marginal improvement of PACG detection.

COL11A1 Polymorphisms Are Associated with Primary Angle-Closure Glaucoma Severity.

Purpose PLEKHA7 and COL11A1 were genotyped for single-nucleotide polymorphisms (SNPs) to investigate the possible association of these two genes with primary angle-closure glaucoma (PACG) and disease severity. Method A total of 51 PACG cases and 51 normal controls were recruited. Twelve SNPs in the PLEKHA7 (rs216489, rs1027617, rs366590, rs11024060, rs6486330, rs11024097, and rs11024102) and COL11A1 (rs1676484, rs3753841, rs12138977, rs2126642, and rs2622848) genes were genotyped by direct Sanger sequencing. Distributions of allele frequencies and genotype frequencies in cases and controls, as well as in mild, moderate, and severe subgroups, were compared based on mean defect (MD ≤ 6.00 dB, 6 dB < MD ≤ 12 dB, and MD > 12 dB were considered mild, moderate, and severe, respectively). Independent Student's t-tests and chi-square tests were used to compare characteristics of PACG cases and controls. Chi-square tests were used to compare the distribution of allele frequencies in cases and controls and in MD-based subgroups with various degrees of glaucoma severity. Binary logistic regression was used to compare the distribution of genotype frequencies and calculate odds ratios (OR) with confidence intervals (CI). Result Three of the 12 SNPs in COL11A1, rs1676486 (P=0.026, OR = 2.089, 95% CI = 1.092–3.996), rs3753841 (P=0.036, OR = 1.886, 95% CI = 1.038–3.426), and rs12138977 (P=0.024, OR = 2.133, 95% CI = 1.104–4.123) were found to have a significant association with PACG. Furthermore, in the subgroup analysis, rs1676486 (P=0.018, OR = 2.416, 95% CI = 1.284–4.544; P=0.011, OR = 2.119, 95% CI = 1.204–3.729), rs12138977 (P=0.009, OR = 2.158, 95% CI = 1.287–3.618; P=0.006, OR = 1.962, 95% CI = 1.239–3.106), and rs3753841 (P=0.007, OR = 2.550, 95% CI = 1.344–4.839) showed statistically significant differences between moderate/severe groups and controls. Conclusion Our data suggested that COL11A1 rs1676484, rs3753841, and rs12138977 polymorphisms may be of value for further study as potential gene-dependent risk factors for developing PACG. Moreover, COL11A1 rs1676484 and rs12138977 polymorphisms might be associated with PACG disease severity.

Genetic association of -1562C&gt;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.

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.

Distinct iris gene expression profiles of primary angle closure glaucoma and primary open angle glaucoma and their interaction with ocular biometric parameters.

BackgroundThis study aimed to evaluate differences in iris gene expression profiles between primary angle closure glaucoma (PACG) and primary open angle glaucoma (POAG) and their interaction with biometric characteristics.DesignProspective study.ParticipantsThirty‐five subjects with PACG and thirty‐three subjects with POAG who required trabeculectomy were enrolled at the Singapore National Eye Centre, Singapore.MethodsIris specimens, obtained by iridectomy, were analysed by real‐time polymerase chain reaction for expression of type I collagen, vascular endothelial growth factor (VEGF)‐A, ‐B and ‐C, as well as VEGF receptors (VEGFRs) 1 and 2. Anterior segment optical coherence tomography (ASOCT) imaging for biometric parameters, including anterior chamber depth (ACD), anterior chamber volume (ACV) and lens vault (LV), was also performed pre‐operatively.Main Outcome MeasuresRelative mRNA levels between PACG and POAG irises, biometric measurements, discriminant analyses using genes and biometric parameters.Results COL1A1, VEGFB, VEGFC and VEGFR2 mRNA expression was higher in PACG compared to POAG irises. LV, ACD and ACV were significantly different between the two subgroups. Discriminant analyses based on gene expression, biometric parameters or a combination of both gene expression and biometrics (LV and ACV), correctly classified 94.1%, 85.3% and 94.1% of the original PACG and POAG cases, respectively. The discriminant function combining genes and biometrics demonstrated the highest accuracy in cross‐validated classification of the two glaucoma subtypes.ConclusionsDistinct iris gene expression supports the pathophysiological differences that exist between PACG and POAG. Biometric parameters can combine with iris gene expression to more accurately define PACG from POAG.

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

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

Особенности течения первичной закрытоугольной глаукомы, осложненной псевдоэксфолиативным синдромом

Purpose. To investigate the prevalence of pseudoexfoliation syndrome (PES) in primary angle-closure glaucoma (PACG) and the nature of changes in ocular structures in process of PES progression to determine the choice of pathogenically oriented treatment. Material and methods. For this investigation 220 Uzbek patients (358 eyes) with hyperopic type of eyes (axial length was 22.8 mm and less) have been selected. The main group included 176 patients (286 eyes) with PACG and different degrees of lens opacity. The comparative group consisted of 44 patients (72 eyes) without PACG and clinical PES symptoms, and with analogous lens opacity. The average age was not statistically significant in both groups and was 58.6±1.2 and 56.4±1.4 years, respectively. All patients underwent complete ophthalmologic examinations. Ultrasound biomicroscopy (UBM) was the basic method of investigation using the model 840 (Zeiss-Humphrey Instruments). The measurements were performed in the superior, lateral, inferior, and medial segments of iridocilliary zone. Results. The UBM method allowed to detect PES symptoms in 64.5% of PACG cases even in absence of clinical PES symptoms. The presence of flakes of pseudoexfoliative material of different echo-density was found on structures of iridocilliary zone with its insufficiency. The pseudoexfoliative flakes were associated with a ciliary zonule fiber weakness. Difference of cilliary zonule fibers length differed by 0.2-0.7mm in various segments of measurement. In these cases an alteration of space correlation between iridocilliary structures took place. The asymmetry of iridocilliary structure parameters and disturbance of their topographic relationships detected by the UBM in PES cases with zonules damage lead to a combination of intraocular blocks in one eye in PACG cases. In segments of cilliary zonule fibers stretching (0.68±0.02mm) the UBM reflected a pattern of segmental relative pupillary block. In opposite segment a sharp reduction of visualized cilliary zonule fibers (0.27±0.02mm) was revealed. The UBM reflected a pattern of plateau iris syndrome. In other situations there was observed a combination the pupillary block and the block induced by the crystalline lens. Conclusion. The results of investigations using the UBM method in Uzbek patients showed that the PES was accompanied with PACG in the absence of clinical signs of disease. The PES was accompanied by alterations of topographic relationships of iridocilliary zonule structures in PACG eyes and promoted in these situations an appearance of intraocular blocks combination: relative pupillary block, block of plateau iris syndrome and crystalline lens block that requires a differentiated approach to the choice of pathogenetic treatment tactics of PACG.

MTHFR C677T predisposes to POAG but not to PACG in a North Indian population: a case control study.

Hyperhomocysteinemia induced by the C677T genetic variant in MTHFR (methylenetetrahydrofolate reductase) has been implicated in neuronal cell death of retinal ganglion cells (RGC), which is a characteristic feature of glaucoma. However, association of MTHFR C677T with glaucoma has been controversial because of inconsistent results across association studies. Association between MTHFR C677T and glaucoma has not been reported in Indian population. Therefore, with a focus on neurodegenerative death of RGC in glaucoma, the current study aimed to investigate association of MTHFR C677T with Primary Open Angle Glaucoma (POAG) and Primary Angle Closure Glaucoma (PACG) in a North Indian population. A total of 404 participants (231 patients and 173 controls) were included in this study. Genotyping was performed by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism. A few random samples were also tested by direct sequencing. Genotypic and allelic distributions of the POAG and PACG cohorts were compared to that of controls by chi-square test and odds ratios were reported with 95% confidence intervals. Genotypic and allelic distributions between POAG cases and controls were significantly different (p = 0.03 and p = 0.01 respectively). Unlike POAG, we did not find significant difference in the genotypic and allelic distributions of C677T between PACG cases and controls (p>0.05). We also observed a higher proportion of TT associated POAG in females than that in males. However, this is a preliminary indication of gender specific risk of C677T that needs to be replicated in a larger cohort of males and females. The present investigation on MTHFR C677T and glaucoma reveals that the TT genotype and T allele of this polymorphism are significant risk factors for POAG but not for PACG in North Indian population. Ours is the first report demonstrating association of MTHFR C677T with POAG but not PACG in individuals from North India.

Global Prevalence of Glaucoma and Projections of Glaucoma Burden through 2040: A Systematic Review and Meta-Analysis

Glaucoma is the leading cause of global irreversible blindness. Present estimates of global glaucoma prevalence are not up-to-date and focused mainly on European ancestry populations. We systematically examined the global prevalence of primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG), and projected the number of affected people in 2020 and 2040. Systematic review and meta-analysis. Data from 50 population-based studies (3770 POAG cases among 140,496 examined individuals and 786 PACG cases among 112 398 examined individuals). We searched PubMed, Medline, and Web of Science for population-based studies of glaucoma prevalence published up to March 25, 2013. Hierarchical Bayesian approach was used to estimate the pooled glaucoma prevalence of the population aged 40-80 years along with 95% credible intervals (CrIs). Projections of glaucoma were estimated based on the United Nations World Population Prospects. Bayesian meta-regression models were performed to assess the association between the prevalence of POAG and the relevant factors. Prevalence and projection numbers of glaucoma cases. The global prevalence of glaucoma for population aged 40-80 years is 3.54% (95% CrI, 2.09-5.82). The prevalence of POAG is highest in Africa (4.20%; 95% CrI, 2.08-7.35), and the prevalence of PACG is highest in Asia (1.09%; 95% CrI, 0.43-2.32). In 2013, the number of people (aged 40-80 years) with glaucoma worldwide was estimated to be 64.3 million, increasing to 76.0 million in 2020 and 111.8 million in 2040. In the Bayesian meta-regression model, men were more likely to have POAG than women (odds ratio [OR], 1.36; 95% CrI, 1.23-1.52), and after adjusting for age, gender, habitation type, response rate, and year of study, people of African ancestry were more likely to have POAG than people of European ancestry (OR, 2.80; 95% CrI, 1.83-4.06), and people living in urban areas were more likely to have POAG than those in rural areas (OR, 1.58; 95% CrI, 1.19-2.04). The number of people with glaucoma worldwide will increase to 111.8 million in 2040, disproportionally affecting people residing in Asia and Africa. These estimates are important in guiding the designs of glaucoma screening, treatment, and related public health strategies.

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

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