Risk Of Primary Angle-closure Glaucoma Research Articles

Mendelian randomization implicates causal association between epigenetic age acceleration and age-related eye diseases or glaucoma endophenotypes

BackgroundAge-related eye diseases (AREDs) have become increasingly prevalent with the aging population, serving as the leading causes of visual impairment worldwide. Epigenetic clocks are generated based on DNA methylation (DNAm) levels and are considered one of the most promising predictors of biological age. This study aimed to investigate the bidirectional causal association between epigenetic clocks and common AREDs or glaucoma endophenotypes.MethodsInstrumental variables for epigenetic clocks, AREDs, and glaucoma endophenotypes were obtained from corresponding genome-wide association study data of European descent. Bidirectional two-sample Mendelian randomization (MR) was employed to explore the causal relationship between epigenetic clocks and AREDs or glaucoma endophenotypes. Multivariable MR (MVMR) was used to determine whether glaucoma endophenotypes mediated the association of epigenetic clocks with glaucoma. Multiple sensitivity analyses were conducted to confirm the robustness of MR estimates.ResultsThe results showed that an increased intrinsic epigenetic age acceleration (HorvathAge) was significantly associated with an increased risk of primary open-angle glaucoma (OR = 1.04, 95% CI 1.02 to 1.06, P = 6.1E−04). The epigenetic age acceleration (EEA) of HannumAge was related to a decreased risk of primary angle-closure glaucoma (OR = 0.92, 95% CI 0.86 to 0.99, P = 0.035). Reverse MR analysis showed that age-related cataract was linked to decreased HannumAge (β = −0.190 year, 95% CI −0.374 to −0.008, P = 0.041). The EEA of HannumAge (β = −0.85 μm, 95% CI −1.57 to −0.14, P = 0.019) and HorvathAge (β = −0.63 μm, 95% CI −1.18 to −0.08, P = 0.024) were associated with decreased central corneal thickness (CCT). PhenoAge was related to an increased retinal nerve fiber layer thickness (β = 0.06 μm, 95% CI 0.01 to 0.11, P = 0.027). MVMR analysis found no mediation effect of CCT in the association of HannumAge and HorvathAge with glaucoma. DNAm-based granulocyte proportions were significantly associated with presbyopia, rhegmatogenous retinal detachment, and intraocular pressure (P < 0.05). DNAm-based plasminogen activator inhibitor-1 levels were significantly related to age-related macular degeneration and intraocular pressure (P < 0.05).ConclusionThe present study revealed a causal association between epigenetic clocks and AREDs. More research is warranted to clarify the potential mechanisms of the biological aging process in AREDs.

Age-related increase in lens thickness and changes in the profile of anterior chamber angle in patients with moderate and high axial hyperopia

PURPOSE. To determine the age-related increase in lens thickness (LT), decrease in anterior chamber depth (ACD) and anterior chamber angle (ACA) in patients with short axial length (APA) of the eyes.METHODS. The study included 100 patients (200 eyes) with short AL (23 mm or less), with a transparent lens or with initial stage of age-related cataract: 46 men and 54 women, aged 19 to 85 years. The LT and ACD, ACA parameters were assessed using optical coherence tomography.RESULTS. In the total population of patients, LT increased by an average of 32 μm per year. At the same time, ACD and ACA decreased by an average of 14 µm and 0.3° per year, respectively (p&lt;0.001). In men, LT increased by 35 μm per year, while in women it increased by 29 μm per year, the difference was not statistically significant (p=0.071). But the decrease in ACA in men averaged 0.38° per year, while in women it was 0.23° per year, this difference was statistically significant (p=0.003). In addition, the rate of decrease in the ACD in men and women also differed statistically significantly: 18 µm versus 11 µm per year (p=0.018).CONCLUSION. 1. According to our data, the annual increase in LT in eyes with short AL averages 32 μm, the decrease in ACD and ACA is on average 14 μm and 0.3° per year, respectively.2. We did not find a statistically significant gender difference in the rate of annual increase in LT, although the rate of decrease in ACA and ACD in men turned out to be statistically significantly higher.3. The obtained data on the annual changes in such morphometric parameters as LT, ACA and ACD in eyes with short AL are key in the formation of primary angle-closure glaucoma (PACG). It may allow a more precise prediction of the timeline of an increased risk of PACG in each particular case.

APOE ε2-Carriers Are Associated with an Increased Risk of Primary Angle-Closure Glaucoma in Patients of Saudi Origin.

This study investigated the association between apolipoprotein E (APOE) gene polymorphisms (rs429358 and rs7412) and primary angle-closure glaucoma (PACG) and pseudoexfoliation glaucoma (PXG) in a Saudi cohort. Genotyping of 437 DNA samples (251 controls, 92 PACG, 94 PXG) was conducted using PCR-based Sanger sequencing. The results showed no significant differences in the allele and genotype frequencies of rs429358 and rs7412 between the PACG/PXG cases and controls. Haplotype analysis revealed ε3 as predominant, followed by ε4 and ε2 alleles, with no significant variance in PACG/PXG. However, APOE genotype analysis indicated a significant association between ε2-carriers and PACG (odds ratio = 4.82, 95% CI 1.52-15.26, p = 0.007), whereas no notable association was observed with PXG. Logistic regression confirmed ε2-carriers as a significant predictor for PACG (p = 0.008), while age emerged as significant for PXG (p < 0.001). These findings suggest a potential role of ε2-carriers in PACG risk within the Saudi cohort. Further validation and larger-scale investigations are essential to elucidate the precise role of APOE in PACG pathogenesis and progression.

Particular Anatomy of the Hyperopic Eye and Potential Clinical Implications.

Background and Objectives: Hyperopia is a refractive error which affects cognitive and social development if uncorrected and raises the risk of primary angle-closure glaucoma (PACG). Materials and Methods: The study included only the right eye-40 hyperopic eyes in the study group (spherical equivalent (SE) under pharmacological cycloplegia over 0.50 D), 34 emmetropic eyes in the control group (SE between -0.50 D and +0.50 D). A complete ophthalmological evaluation was performed, including autorefractometry to measure SE, and additionally we performed Ocular Response Analyser: Corneal Hysteresis (CH), Corneal Resistance Factor (CRF); specular microscopy: Endothelial cell density (CD), Cell variability (CV), Hexagonality (Hex), Aladdin biometry: Anterior Chamber Depth (ACD), Axial Length (AL), Central Corneal Thickness (CCT). IBM SPSS 26 was used for statistical analysis. Results: The mean age of the entire cohort was 22.93 years (SD ± 12.069), 66.22% being female and 33.78% male. The hyperopic eyes had significantly lower AL, ACD, higher SE, CH, CRF. In the hyperopia group, there are significant, negative correlations between CH and AL (r -0.335), CRF and AL (r -0.334), SE-AL (r -0.593), ACD and CV (r -0.528), CV and CRF (r -0.438), CH (r -0.379), and positive correlations between CCT and CH (r 0.393) or CRF (r 0.435), CD and ACD (r 0.509) or CH (0.384). Age is significantly, negatively correlated with ACD (r -0.447), CH (r -0.544), CRF (r -0.539), CD (r -0.546) and positively with CV (r 0.470). Conclusions: Our study suggests a particular biomechanical behavior of the cornea in hyperopia, in relation with morphological and endothelial parameters. Moreover, the negative correlation between age and ACD suggests a shallower anterior chamber as patients age, increasing the risk for PACG.

Genetic and Environmental Contributions of Primary Angle-Closure Glaucoma and Primary Open-Angle Glaucoma: A Nationwide Study in Taiwan

PurposeTo estimate the familial risks of primary angle-closure glaucoma (PACG) and primary open-angle glaucoma (POAG) and assess the relative contributions of environmental and genetic factors to these risks. DesignRetrospective, population-based cohort study. MethodsWe used the 2000-2017 Taiwan National Health Insurance Program database to construct 4,144,508 families for the 2017 population (N=23,373,209). We used the polygenic liability model to estimate glaucoma's heritability and familial transmission. The degree of familial aggregation of glaucoma was obtained from the adjusted relative risk for individuals whose first-degree relatives had glaucoma using Cox's model. ResultsPACG and POAG prevalence rate for individuals whose first-degree relatives had PACG or POAG was 0.95% and 2.40%, higher than those of the general population (0.61% and 0.40%, respectively). The relative risk of PACG in individuals whose first-degree relatives had PACG was 2.44 (95%CI=2.31-2.58). The relative risk of POAG in individuals whose first-degree relatives had POAG was 6.66 (95%CI=6.38-6.94). The estimated contributions to PACG and POAG phenotypic variances were 19.4% and 59.6% for additive genetic variance, 19.1% and 23.2% for common environmental factors shared by family members, and 61.5% and 17.2% for non-shared environmental factors, respectively. ConclusionsThese data highlight the relative importance of genetic contribution to POAG and environmental contribution to PACG. Therefore, future work may need to focus on finding more novel environmental determinants of PACG.

Genetic associations in CHAT and COL11A1 with primary angle-closure glaucoma susceptibility: A systematic review and meta-analysis.

Genome-wide association studies (GWAS) have identified that single-nucleotide polymorphisms (SNPs) rs1258267 in CHAT and rs3753841 in COL11A1 are associated with primary angle-closure glaucoma (PACG). The purpose of the study was to evaluate the association of CHAT rs1258267 and COL11A1 rs3753841 with PACG. A comprehensive electronic database search was performed to include eligible studies, published from October 2010 to March 2022. By calculating summary odds ratios (ORs) and 95% confidence intervals (CI) under five genetic models, the risk of PACG related to these two SNPs could be estimated. Heterogeneity was measured with a Chi-square-based Q statistic test and the I2 statistic. By the Z test, we analyzed the overall effect of OR. We used funnel plots and Begg's funnel plots to evaluate the publication bias of included studies. The meta-analysis was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 checklist. There were eighteen studies associating CHAT rs1258267 with PACG indicating evidently decreased PACG risk in five genetic models. Thirty studies were included to demonstrate a notable increase in the risk of PACG-carrying COL11A1 rs3753841 genotypes. Subgroup analyses showed that the association of CHAT rs1258267 and COL11A1 rs3753841 with PACG was obvious in Asians, while no evidence was found to confirm this connection in Caucasians. This meta-analysis suggests that CHAT rs1258267 G/A polymorphisms could bring about a decreased risk of PACG susceptibility and COL11A1 rs3753841 G/A polymorphisms could cause an increased risk. These effects mainly manifest in Asians.

Технические трудности выполнения миниинвазивной хирургии катаракты при утолщенном хрусталике в глазах с короткой переднезадней осью

Purpose. To study the technical features of cataract phacoemulsification in in eye with short axial length. Material and methods. 18 eyes with an increased risk of primary angle-closure glaucoma (PACG) (18 patients, age: 46–80 years). In 14 eyes – clear lens; 4 eyes – initial cataract. Phacoemulsification for prophylaxis of development of PACG is carried out. Features of surgical technique and complication are revealed. The term of observation was 12–36 months. Results. Improvement of anatomic parameters of eye globe and visual functions is reached; PACG did not develop at anybody in remote period of observation. Conclusion. High performance and safety phacoemulsification of transparent crystalline lens for prophylaxis of risk of development of an acute attack of PACG in eyes with the short axial lengths is proved. Keywords: hyperopia, angle-closure glaucoma, phacoemulsification, complications.

Rates and Patterns of Diagnostic Conversion from Anatomical Narrow Angle to Primary Angle-Closure Glaucoma in the United States

To assess rates of diagnostic conversion from anatomical narrow angle (ANA) to primary angle-closure glaucoma (PACG) in the United States and identify factors associated with diagnostic conversion. Retrospective case-control study. Patients diagnosed with ANA between the years 2007 and 2019 were identified based on International Classification of Diseases (ICD) codes in the Optum Clinformatics Data Mart Database. Inclusion was limited to newly diagnosed ANA, defined as the following: (1) continuous enrollment during a 2-year look back period and 6-year study period from index (first) date of ANA diagnosis; (2) diagnosis by an ophthalmologist or optometrist and record of gonioscopy; and (3) no history of intraocular pressure (IOP)-lowering drops, laser peripheral iridotomy (LPI), or intraocular surgery. Cox proportional hazards models were developed to assess factors associated with diagnostic conversion, defined as a change in ICD code from ANA to PACG. New diagnosis of PACG within the 6-year study period recorded after an index diagnosis of ANA. Among 3985 patients meeting inclusion criteria, 459 (11.52%) had detected diagnostic conversion to PACG within the study period. The conversion rate was stable at 3.54% per year after the first 6 months of ANA diagnosis. In the Cox proportional hazards model, age > 70 years and early (within 6 months of ANA diagnosis) need for LPI or IOP-lowering drops were positively associated with diagnostic conversion (hazard ratio [HR] > 1.59; P < 0.02). Cataract surgery at any time and late (after 6 months of ANA diagnosis) need for IOP-lowering drops appeared protective against diagnostic conversion (HR < 0.46; P < 0.004). Annual risk of diagnostic conversion from ANA to PACG is relatively low overall; elderly patients are at higher risk whereas patients receiving cataract surgery are at lower risk. The utility of long-term monitoring seems low for most patients with ANA, highlighting the need for improved clinical methods to identify patients at higher risk for PACG. Proprietary or commercial disclosure may be found after the references.

Impact of rs11024102 PLEKHA7, rs3753841 COL11A1 single nucleotide polymorphisms, and serum levels of oxidative stress markers on the risk of primary angle-closure glaucoma in Egyptians

BackgroundPrimary angle-closure glaucoma (PACG) is one of the major causes of blindness in the Middle East with genetic loci and systemic oxidative stress as potential risk factors. The current case-control study aimed to investigate the associations of rs11024102 in Pleckstrin homology domain-containing family A member 7 (PLEKHA7), rs3753841 in collagen 11 A1 (COL11A1), and the systemic oxidative stress markers with PACG in Egyptian patients. Thirty-five control subjects and 64 PACG patients were enrolled in this study. The polymorphisms in PLEKHA7 and COL11A1 were analyzed using quantitative PCR, and their associations were statistically tested with PACG at homozygous, heterozygous, dominant, and recessive genetic models. The levels of malondialdehyde (MDA), advanced glycation-end product (AOPP), protein carbonyl (PC), and ischemia modified albumin (IMA) were quantitated colorimetrically, and their associations with PACG were analyzed statistically. The associations of MDA, AOPP, PC, and IMA with elevated intraocular pressure (IOP) were statistically tested. ResultsNeither significant difference in the genotype distribution nor allele frequency of PLEKHA7 11024102 T>C (p = 0.425 and 0.517, respectively) and COL11A1 rs3753841 G>A (p = 0.600 and 0.473, respectively) were recorded under any of the tested genetic models. Either rs11024102 PLEKHA7 or rs3753841 COL11A1 was not significantly (p > 0.025 after Bonferroni correction) associated with an increased risk of PACG in Egyptians. Egyptian patients with PACG showed significant elevations in the serum levels of MDA, AOPP, and PC either in patients with or without cases with diabetes mellites, hypertension, coronary vascular diseases, and smoking. Serum levels of MDA, AOPP, and PC were significantly associated with PACG in Egyptians (p < 0.013 after Bonferroni correction). However, MDA and PC only showed significant associations with the elevation in the IOP (p = 0.007 and 0.045, respectively) in PACG patients. ConclusionBoth rs11024102 and rs3753841 could not be considered as potential gene-dependent risk factors for PACG pathogenesis in Egyptians. On the other hand, serum levels of MDA, AOPP, and PC might be considered risk factors for PACG. Moreover, MDA and PC could serve as good predictors for the elevation of the IOP in PACG disease.

A comparison of lens parameters in patients with various subtypes of primary angle-closure disease and the normal population: A prospective study.

To assess the role of lens parameters in the detection and progression of primary angle-closure disease (PACD) by combining A-scan and A-scan optical coherence tomography (AS-OCT) parameters. A cross-sectional study was conducted in a tertiary health-care center in eastern India. A total of 91 study subjects including cases and controls were included in the study. The parameters studied were lens thickness (LT), lens axial factor (LAF), relative lens position (RLP), and lens vault (LV). Anterior chamber depth (ACD) and axial length (AL) were also analyzed using A-scan. The LT was significantly more in all subtypes of PACD (from 4.24 ± 0.84 to 5.02 ± 0.18 mm) than in controls (4.04 ± 0.46 mm; P < 0.01). Similarly, LAF was significantly less among all subtypes of PACD compared to controls (P < 0.001). The RLP, calculated using the formula (ACD + 0.5 LT)/AL × 10, showed no significant difference (P > 0.05) between various study groups. The LV in acute angle-closure glaucoma (AcCG) patients was significantly higher compared to the control population (P < 0.01). Ocular parameters like ACD decreased, whereas LT and LAF increased from normal through primary angle closure (PAC) to primary angle-closure glaucoma (PACG). Logistic regression analysis found a significant association between a decrease in ACD and an increased risk of PACG (P-value was 0.0001) and an increase in LT and LAF with increased risk of PACG (P = 0.040 and P = 0.006, respectively). Inclusion of lens parameter assessment in the workup of a patient with PACD helps in detection and close monitoring of the progression from suspected to disease state.

In vivo biomechanical assessment of iridial deformations and muscle contractions in human eyes.

The iris is a muscular organ whose deformations can cause primary angle-closure glaucoma (PACG), a leading cause of blindness. PACG risk assessment does not consider iridial biomechanical factors, despite their expected influence on iris deformations. Here, we exploited an existing biometric dataset consisting of near-infrared movies acquired during the pupillary light reflex (PLR) as a unique resource to study iris biomechanics. The PLR caused significant (greater than 100%) and essentially spatially uniform radial strains in the iris in vivo, consistent with previous findings. Inverse finite-element modelling showed that sphincter muscle tractions were ca fivefold greater than iridial stroma stiffness (range 4- to 13-fold, depending on sphincter muscle size). This muscle traction is greater than has been previously estimated, which may be due to methodological differences and/or to different patient populations in our study (European descent) versus previous studies (Asian); the latter possibility is of particular interest due to differential incidence rates of PACG in these populations. Our methodology is fast and inexpensive and may be a useful tool in understanding biomechanical factors contributing to PACG.

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.

Выявление случаев повышенного риска первичной закрытоугольной глаукомы у молодых пациентов с высокой степенью гиперметропии

Purpose. Evaluation of the incidence of risk of primary angle-closure glaucoma (PACG) in young patients with a high hyperopia. Material and methods. The main group consisted of 58 healthy patients (116 eyes) with high hyperopia. Their age ranged from 32 to 40 years. Selection criteria: the anteroposterior axis (APA) of the eye is less than 22 mm, the absence of ophthalmic and systemic somatic pathology. The comparison group was formed by 52 patients (104 eyes) with high hyperopia (APA less than 22 mm) and the initial stage of PACG, as well as the presence of a functional block of the front camera angle. Their age ranged from 45 to 50 years with a median of 47 years. The morphometric parameters of the anterior segment of the eyes were evaluated in groups. Results. We determined statistically significant differences in all studied parameters of the compared groups: the depth of the anterior chamber in the central zone, the thickness of the lens, the volume of the anterior chamber. However, when comparing these indicators with the comparison group, it was found that in 15 patients in the main group, most of them were comparable. Conclusion. Comparative analysis of the topographic and anatomical parameters of the anterior segment of the eyes of young healthy hypermetropes made it possible to identify 15 people. (26 %) with an increased risk of developing PACG and an acute attack. Keywords: acute attack of angle-closure glaucoma, hyperopic refraction, anteroposterior axis of the eye, lens thickness, anterior chamber depth, anterior chamber volume.

Evaluation of ABCA1 and FNDC3B Gene Polymorphisms Associated With Pseudoexfoliation Glaucoma and Primary Angle-Closure Glaucoma in a Saudi Cohort.

Objective: It is plausible that common disease mechanisms exist in glaucoma pathophysiology. Accordingly, we investigated the genetic association of two previously reported primary open-angle glaucoma (POAG)-related gene polymorphisms, rs2472493 (A > G) in ABCA1 and rs7636836 (C > T) in FNDC3B, in primary angle-closure glaucoma (PACG) and pseudoexfoliation glaucoma (PXG). Methods: TaqMan genotyping was performed in a total of 442 subjects consisting of 246 healthy controls, 102 PACG patients, and 94 PXG patients. Statistical evaluations were performed to detect allelic and genotype association of the variants with the disease and clinical variables such as intraocular pressure (IOP) and cup/disc ratio. Results: Overall, there was no allelic or genotype association of these variants in PACG and PXG. However, rs7636836[T] allele significantly increased the risk of PXG among men (p = 0.029, odds ratio [OR] = 2.69, 95% confidence interval = 1.11–6.51). Similarly, rs2472493 and rs7636836 genotypes also showed significant association with PXG among men in over-dominant model (p = 0.031, OR = 1.98, 95% CI = 1.06–3.71) and co-dominant model (p = 0.029, OR = 2.69, 95% CI = 1.11–6.51), respectively. However, none survived Bonferroni’s correction. Besides, the synergic presence of rs2472493[G] and rs7636836[T] alleles (G-T) was found to significantly increase the risk of PACG (p = 0.026, OR = 2.85, 95% CI = 1.09–7.46). No significant genotype influence was observed on IOP and cup/disc ratio. Conclusion: Our results suggest that the polymorphisms rs2472493 in ABCA1 and rs7636836 in FNDC3B genes may be associated with PXG among men, and a G-T allelic combination may confer an increased risk of PACG in the middle-eastern Saudi cohort. Further research in a larger population-based sample is needed to validate these findings.

Six-Year Incidence and Risk Factors for Primary Angle-Closure Disease: The Singapore Epidemiology of Eye Diseases Study

To determine the incidence and risk factors of primary angle-closure disease (PACD) over 6 years in a multi-ethnic Asian population. Population-based, longitudinal study. The Singapore Epidemiology of Eye Diseases study is a population-based cohort study conducted among adults aged 40 years or more. The baseline examination was conducted between 2004 and 2010, and the 6-year follow-up visit was conducted between 2011 and 2017. Of 6762 participants who attended the follow-up examination, 5298 at risk for primary angle-closure glaucoma (PACG) and 5060 at risk for PACD were included for analyses. Standardized examinations including slit-lamp biomicroscopy, indentation gonioscopy, intraocular pressure (IOP) measurement, and static automated perimetry were performed. In this study, PACD includes primary angle-closure suspect (PACS), primary angle-closure (PAC), and PACG. The 6-year PACD incidence was evaluated among an at-risk population excluding adults with baseline glaucoma, PACS, PAC, pseudophakia at baseline or follow-up, or laser peripheral iridotomy or iridectomy at baseline visit. Logistic regression analysis adjusting for age, gender, and ethnicity was performed to evaluate associations between PACD development and demographic or ocular characteristics. Forward selection based on the Quasi-likelihood Information Criterion was used in multivariable analysis to reduce potential multicollinearity. The 6-year age-adjusted PACD incidence was 3.50% (95% confidence interval [CI], 2.94-4.16). In multivariable analysis, increasing age per decade (odds ratio [OR], 1.35; 95% CI, 1.15-1.59), higher IOP (OR, 1.04; 95% CI, 1.00-1.08), and shallower anterior chamber depth (OR, 1.11; 95% CI, 1.08-1.14) at baseline were associated with higher odds of PACD, whereas late posterior subcapsular cataract (PSC) (OR, 0.60; 95% CI, 0.48-0.76) was associated with lower odds of PACD. The 6-year age-adjusted incidences of PACG, PAC, and PACS were 0.29% (95% CI, 0.14-0.55), 0.46% (95% CI, 0.29-0.75), and 2.54% (95% CI, 2.07-3.12), respectively. Our study showed that the 6-year incidence of PACD was 3.50%. Increasing age, higher IOP, and shallower anterior chamber were associated with a higher risk of incident PACD, whereas late PSC was associated with a lower odds of PACD. These findings can aid in future projections and formulation of health care policies for screening of at-risk individuals for timely intervention.

Genetic Markers PLEKHA7, ABCC5, and KALRN Are Not Associated With the Progression of Primary Angle Closure Glaucoma (PACG) in Malays.

IntroductionPLEKHA7, ABCC5, and KALRN have been identified as susceptible genetic markers related to glaucoma. We aimed to investigate the association between the identified susceptible genetic markers PLEKHA7 rs11024102, ABCC5 rs17217796, and KALRN rs1392912 in the progression of primary angle-closure glaucoma (PACG) in Malay patients.MethodsFor this study, 163 Malay patients with PACG were recruited from April 2015 to April 2017 at Hospital Universiti Sains Malaysia and Hospital Raja Perempuan Zainab II, Kota Bharu. Venesection was performed. DNA was extracted using a commercial DNA extraction kit. The primer was optimized for rs11024102, rs17217796, and rs1392912 of the PLEKHA7, ABCC5, and KALRN genes, respectively. Polymerase chain reaction (PCR) was performed, and PCR products were purified. A DNA sequencer was used to identify polymorphisms. Progression was based on the agreement between the Advanced Glaucoma Intervention Study scoring system and the Hodapp-Parrish and Anderson staging system. The scoring was conducted on two reliable consecutive Humphrey visual fields (HVFs) during the recruitment period and two baseline HVFs obtained when the diagnosis was made. Based on the scoring, patients were grouped into progressed and non-progressed. A chi-square test was used to analyze the association between the genetic markers and the progression of PACG.ResultsOne hundred and sixty-three Malay patients with PACG (58 men and 105 women) were recruited. Twenty-nine patients (18%) had visual field progression of PACG after a mean (SD) follow-up of 6.0 (1.0) years. The minor allele frequencies for PLEKHA7 rs11024102 (G/A), ABCC5 rs17217796 (C/G), and KALRN rs1392912 (A/G) were 0.44, 0.08, and 0.48, respectively. We found that rs11024102 (p=0.828), rs17217796 (p=0.865), and rs1392912 (p=0.684) were not associated with PACG progression in the Malay patients.ConclusionAlthough PLEKHA7 and ABCC5 were found to be genetic markers associated with the risk of PACG, they played no roles in PACG progression in the Malay population. Moreover, KALRN was not significantly associated with PACG progression. Other susceptible genetic markers may be responsible for PACG progression.

Nationwide Glaucoma incidence in end stage renal disease patients and kidney transplant recipients

Glaucoma shares common risk factors with chronic kidney disease (CKD) but previous cross-sectional studies have demonstrated discrepancies in the risk of glaucoma in CKD patients. This study enrolled kidney transplantation recipients (KTRs) (n = 10,955), end stage renal disease (ESRD) patients (n = 10,955) and healthy controls (n = 10,955) from National Health Insurance Service database of the Republic of Korea. A Cox proportional hazard regression model was used to calculate the hazard ratios (HR) for primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG) incidences. The incidence of POAG was higher in ESRD patients (3.36/1,000 person-years, P < 0.0001) and KTRs (3.22 /1,000 person-years, P < 0.0001), than in healthy controls (1.20/1,000 person-years). However, POAG risk showed no significant increase in either ESRD patients (P = 0.07) or KTRs (P = 0.08) when adjusted for the confounding factors. The incidence of PACG was significantly higher in ESRD patients (0.41/1,000 person-years) than in healthy controls (0.14/1,000 person-years, P = 0.008). The PACG incidence was significantly lower in KTRs than in ESRD patients (HR = 0.35, P = 0.015). In conclusion, this nationwide cohort study demonstrated that kidney transplantation can reduce the risk of PACG but not POAG in ESRD patients.

Association of Single-Nucleotide Polymorphisms in ABCC5 Gene with Primary Angle Closure Glaucoma and the Ocular Biometric Parameters in a Northern Chinese Population

Background: The rs1401999 gene in ABCC5 gene was the first locus confirmed by a genome-wide association study (GWAS) to be associated with both anterior chamber depth (ACD) and primary angle closure glaucoma (PACG); however, this locus was of obvious heterogeneity among different populations in the GWAS, and the conclusion has not been further verified by other studies. Therefore, this study was carried out to investigate whether the single-nucleotide polymorphisms (SNPs) in ABCC5 gene are associated with PACG and the ocular biometric parameters ACD and axial length (AL) in samples from northern China. Methods: Case-control association study included 500 PACG patients and 720 unrelated controls from northern China, and genotyping was performed for ten SNPs in ABCC5 gene using an improved multiplex ligation detection reaction technique. The association between these SNPs and risk of PACG was estimated by PLINK using a logistic regression model, while the association between genotypes and ocular biometric parameters was performed by SPSS using generalized estimation equation. Results: An SNP rs4148568 (p = 0.046) and a haplotype TCGGAG (p = 0.0364) in ABCC5 were associated with PACG, and rs4148568 was nominally associated with AL (β = 0.092, p = 0.08). Conclusions: The SNP rs4148568 and a haplotype TCGGAG in ABCC5 contribute to PACG in northern Chinese people. In addition, rs4148568 might be associated with the AL, the variant allele of which may have effect of making the AL longer. Further studies are needed to elucidate the exact mechanism of ABCC5 in the progress of PACG.

Association analysis of polymorphisms rs12997 in ACVR1 and rs1043784 in BMP6 genes involved in bone morphogenic protein signaling pathway in primary angle-closure and pseudoexfoliation glaucoma patients of Saudi origin

BackgroundGlaucoma is a polygenic neurodegenerative disease and the second most common cause of blindness in Saudi Arabia. To test the hypothesis that genetic variants in the genes involved in the bone morphogenic protein (BMP) signaling pathway may be associated with glaucoma, we investigated the association between 3′ untranslated region variants, rs12997 in ACVR1 and rs1043784 in BMP6, and primary angle-closure glaucoma (PACG) and pseudoexfoliation glaucoma (PXG).MethodsIn a case-control study, TaqMan® real-time PCR-based genotyping was done in 444 subjects consisting of 250 controls, 101 PACG and 95 PXG cases, and tested for genetic association with glaucoma-types and other clinical phenotypes.ResultsRs12997[G] allele in ACVR1 exhibited significant 2-fold increased risk of PACG (p = 0.005) in women but not in men. Similarly, genotype analysis also showed that subjects carrying rs12997[G/G] genotype were at > 2-fold risk of PACG that remained significant after adjustment for age, sex, and Bonferroni correction in the recessive model. Furthermore, this effect was also significant in women only. In PXG, the rs12997[G/G] genotype showed a significant trend towards increased risk of the disease (OR = 2.04, 95% CI = 0.99–4.18, p = 0.049) but did not survive the Bonferroni correction. Regression analysis showed that rs12997[G/G] genotype was a significant predictor of PACG independent of age, sex, and rs1043784 genotypes. Likewise, age and rs12997[G/G] genotype showed significant effect on PXG outcome. The rs12997[A/G] genotype showed significant association with cup/disc ratio as compared to wild-type (p = 0.005) in PXG. Genotype and allele frequencies of rs1043784 in BMP6 did not show any significant association either with PACG or PXG.ConclusionsOur results suggest that the polymorphism rs12997 in the ACVR1 gene involved in the BMP signaling pathway is significantly associated with PACG and PXG in a Saudi cohort. This is the first study to associate this variant/gene with PACG and PXG. However, further studies would be needed to replicate these findings in a large population-based cohort.

The prevalence of diabetes among male glaucoma patients

Introduction: The purpose of this study was to examine the relationship between diabetes and glaucoma.Methods: Consecutive 143 subjects with primary angle-closure glaucoma and 127 subjects with primary open-angle glaucoma (control) were studied retrospectively at an urban Veterans Administration Hospital. In addition to ocular examination findings, body mass index (BMI) and diabetes mellitus (DM) status were recorded.Results: All subjects in this study were male. The mean age was 72.3 years old in primary open angle versus 71.1 in primary angle-closure subjects. Half of the subjects with angle closure and 70% of open-angle subjects were self-identified as African–American. BMI was not significantly different between the two groups (28.2 in open angle vs. 28.7 in angle closure; P = 0.45). The percentage of DM was higher in subjects with primary angle closure than in those with primary open-angle glaucoma (43% vs. 29%, P = 0.001; Chi-square test). The odds of having DM were nearly two times higher in angle-closure subjects than open-angle subjects (Logistic regression, P = 0.01, 95% confidence interval: 1.17–3.30).Conclusion: In this retrospective study, diabetes was found to be associated with higher risk for primary angle-closure glaucoma.