Myocilin mt.1 gene promoter single nucleotide polymorphism (-1000C>G) in Brazilian patients with primary open angle glaucoma

Background: The myocilin (MYOC) gene promoter polymorphism -1000C>G (MYOC mt.1) can be associated with faster progression of primary open angle glaucoma (POAG). The purpose of this study was to investigate the MYOC mt.1 in Brazilian patients with POAG and to evaluate its possible role on the phenotype and the severity of the disease.

Material and methods: One hundred sixty-seven POAG patients and 130 normal controls were enrolled. DNA samples were prepared and the MYOC mt.1 polymorphism was screened by real-time polymerase chain reaction (RT – PCR) in an Single-nucleotide polymorphism (SNP) assay. Frequencies of the MYOC mt.1 promoter polymorphism were determined for both groups and compared by Fisher’s exact test and Chi-square test with Yate’s correction. Intraocular pressure (IOP), cup-to-disc ratio (C/D), number of glaucoma medications, and number of glaucoma surgeries were compared between MYOC mt.1 carriers and non-carriers.

Results: MYOC mt.1 genotype frequencies did not differ between POAG and controls (P = 0.420); 14.6% of controls and 16.4% of POAG patients were MYOC mt.1 carriers (CG or GG). Frequencies of the G allele were similar between glaucomatous patients and controls (7.3% and 9.2%, respectively; P = 0.477). Among POAG patients, there were no differences in mean C/D ratio, IOP, number of glaucoma medications, and surgical procedures for IOP control between carries and non-carriers of the MYOC mt.1 promoter polymorphism (p>0.05).

Conclusion: The G allele of the MYOC mt.1 promoter polymorphism was equally distributed among POAG patients and healthy subjects and it is possibly unrelated to the risk and severity of disease in the Brazilian population.     

一青光眼大家系的致病基因筛查研究

目的：为了了解青光眼的可能致病基因,我们对一青光眼大家系致病基因进行了筛查研究。

方法：采集外周血和绘制家系图,提取患者全基因组DNA,PCR扩增目的基因MYOC,CYP1B1,OPTN,WDR36的外显子并鉴定,测序后进行数据分析,与数据库中相应参考序列进行比对。通过基于目标区域捕获技术的眼科基因定制芯片对家系样本进行了测序分析,希望能鉴定该家系的致病基因或发现新的致病位点。

结果：对该家系进行已知青光眼候选基因MYOC,CYP1B1,WDR36,OPTN测序分析及目标区域捕获技术的眼科基因定制芯片分析,并经家系内其他患者及正常成员测序验证,排除了已知青光眼候选基因突变,仅发现了5个多态性位点。

结论：青光眼属多基因遗传疾病,已知致病基因并不能覆盖所有青光眼,推测可能存在某些我们目前尚不知道的青光眼致病基因,本青光眼家系的致病基因有待进一步研究。     

Occurrence of MYOC and CYP1B1 variants in juvenile open angle glaucoma Brazilian patients

ABSTRACT

Background: The purpose of this study was to screen juvenile open angle glaucoma (JOAG) patients from Brazil for variants within the MYOC and CYP1B1 genes.

Material and Methods: In this study, we evaluated the coding regions of MYOC and CYP1B1 genes in 100 non-related patients with JOAG and 200 controls through Sanger sequencing. We also tested the most frequent single nucleotide variants of CYP1B1 for association with JOAG.

Results: Sixteen different sequence variants in the MYOC gene were observed in JOAG patients: eight variants were described as neutral and eight were identified in 34 out of 100 patients with JOAG and no controls, thus being considered damaging. In the CYP1B1 gene, nine neutral variants and two damaging alterations were found among JOAG patients. No association between CYP1B1 variants and JOAG was detected.

Conclusion: While MYOC damaging alterations were highly prevalent (34%), CYP1B1 damaging variants were less frequent (2%) in this cohort of Brazilian JOAG patients.     

Genetic analysis of patients with primary congenital glaucoma

Purpose

To determine the common gene mutation in patients with primary congenital glaucoma (PCG) in the Southeast region of Turkey via genetic analysis and to evaluate whether there were other gene mutations in these patients.

Methods

A total of 25 patients with PCG were included in this study. We performed sequence analysis including all exons of cytochrome p450 1B1 (CYP1B1), myocilin (MYOC), forkhead box C1 (FOXC1), and paired-like homeodomain 2 (PITX2) genes of the obtained samples. Further, we analyzed the results using the Nextgen analysis program.

Results

The CYP1B1 gene mutation was detected in 20 (80%) of 25 patients, and FOXC1 gene mutation was detected in one (4%) patient. The mutation site of nine (45%) of the 20 CYP1B1 genes was found in the second exon. The pathogenic variant (p.Gly61Glu) was observed in 12 (60%) patients (in the first and second exons); the mutation type of six (50%) of these patients was homozygous. The mutation site of one patient with FOXC1 gene mutation was found to be in the first exon; its pathogenic variant was p.Met400lle. The mutation type in this gene was observed to be heterozygous. Lastly, there were no mutations in the MYOC, FOXC1, and PITX2 genes in combination with the CYP1B1 gene mutation.

Conclusion

The most common cause of PCG in our region is the CYP1B1 gene mutation, and the most frequent pathogenic variant is c.182G?>?A (p.Gly61Glu). We also determined that the CYP1B1 gene mutation was alone and did not occur with other gene mutations (MYOC, FOXC1, and PITX2).

     

Automated iris volume analysis and trabecular meshwork length using anterior segment optical coherence tomography - Application in pseudoexfoliation and pseudoexfoliation glaucoma

Purpose:The aim of this study was to evaluate differences in the iris and angle parameters in psuedoexfoliation syndrome (PXF) and pseudoexfoliation glaucoma (PXG) using anterior segment optical coherence tomography (ASOCT).Methods:Patients with PXF or PXG were compared using ASOCT with primary open-angle glaucoma POAG eyes as controls in this noninterventional comparative study conducted at a tertiary eye care center in East India. All angle parameters, TM length, and iris thickness were analyzed from the enhanced depth imaging (EDI) single scans obtained. Quadrant scans were used for the calculation of iris volume using a custom-built in-house software. In particular, the software performs multiple operations including edge detection, connected components, and thresholding to localize and segment the iris. Differences in the iris volume/thickness and TM length in PXF and PXG with POAG were analyzed.Results:A total of 225 eyes were included, which included 75 PXG and 98 PXF cases and 52 POAG with a mean age of 67 ± 9.7 years at presentation. The algorithm repeatability and reproducibility was also established with correlation coefficients more than 99% which was substantiated with Bland-Altman plots. The iris volume (calculated in 197 images of 225 eyes) did not differ significantly in PXF and PXG eyes, although both had significantly greater volume compared to POAG eyes. The iris volume or other angle parameters including TM length did not correlate with clinical variables such as IOP, age, or visual field indices.Conclusion:Iris parameters or TM length do not explain pathogenesis of glaucoma in pseudoexfoliation.     

Comparison of blood flow velocities of the extraocular vessels in patients with pseudoexfoliation or primary open-angle glaucoma.

PURPOSE: To evaluate orbital blood flow velocities in patients with pseudoexfoliation glaucoma (PXG) or primary open-angle glaucoma (POAG). METHODS: Blood flow velocities in the ophthalmic, central retinal, and posterior ciliary arteries were evaluated by color Doppler imaging in 26 patients with PXG, 28 patients with POAG and 30 age-matched normal control subjects. The results were compared. RESULTS: Compared to the control subjects, patients with PXG showed statistically significant decreases in the mean peak systolic and end-diastolic velocities and increased mean resistive indices in all vessels except for the ophthalmic artery mean peak systolic velocity (p < 0.05). Patients with POAG, when compared to the control subjects, showed statistically significant decreases in the mean end-diastolic velocities and increased mean resistive indices in all vessels measured (p < 0.05). No statistically significant differences were found in the mean blood flow parameters between POAG and PXG. CONCLUSION: Blood flow velocities of the retrobulbar vessels are decreased in patients with PXG. Reduced blood flow velocities may be secondary as well as contributory to exfoliative glaucomatous damage. Although there was no significant difference in the mean blood flow parameters between POAG and PXG, alterations of retrobulbar vessels might be associated with different pathogenic mechanisms of PXG.     

Ab interno gel implant in patients with primary open angle glaucoma and pseudoexfoliation glaucoma

Purpose

To compare efficacy and safety results of an ab interno gel implant in patients with pseudoexfoliation glaucoma (PXG) and primary open angle glaucoma (POAG).

Methods

Retrospective analysis of the medical records of 110 consecutive eyes with open angle glaucoma who had received a XEN45 gel implant between March 2014 and June 2015. Intraocular pressure course, number of glaucoma medications, the need for additional intervention (including needling) and complications were evaluated until 12?months postoperatively.

Results

Data of 67 eyes with POAG and 43 eyes with PXG were analyzed. At 12?months postoperatively, the mean IOP had significantly decreased by 54.0% from preoperatively 31.85?±?8.5?mmHg to 13.99?±?2.6?mmHg in the POAG group, (p?=?0.000; Wilcoxon test), and by 55.2% from 31.63?±?9.0?mmHg to 13.28?±?3.1?mmHg in the PXG group (p?=?0.000; Wilcoxon test). The mean number of anti-glaucoma medications had significantly decreased from 3.25?±?0.8 at baseline to 0.3?±?0.7 medications at 12?months postoperatively in POAG eyes (p?=?0.000; Wilcoxon test), and from 3.05?±?1.0 to 0.3?±?0.6 medications in PXG eyes (p?=?0.000; Wilcoxon test). Hypotony (IOP?≤?6?mmHg) was observed in 2 POAG eyes (3.0%) and in 5 PXG eyes (11.7%) at 1?month but normalized in all eyes at 12?months postoperatively. Severe complications were not observed. No statistically significant differences were found between PXG eyes and POAG eyes.

Conclusion

Our data indicate that the XEN45 gel implant provides significant and comparable reduction in IOP and anti-glaucoma medication during the one-year follow-up period in POAG as well as PXG eyes. This suggests that it may be a noteworthy alternative to traditional filtering procedures in patients with POAG and PXG respectively.

     

CYP1B1基因突变与原发性开角型青光眼发病关系的研究进展

原发性青光眼包括原发性开角型青光眼（POAG）、原发性闭角型青光眼（PACG）及原发性婴幼儿青光眼（PCG）.目前认为原发性青光眼的发病是遗传因素、环境因素、生活习惯等多种因素综合作用的结果,其中遗传因素,尤其是基因突变,在青光眼的发病过程中起着重要作用.自1997年发现CYP1B1基因为PCG的致病基因以来,关于CYP1B1基因突变与青光眼发病关系的研究成为青光眼遗传和基因研究的热点.随着研究的逐渐深入,许多学者认为CYP1B1基因也是POAG致病基因的候选基因.本研究对近十余年来对CYP1 B1基因的结构和功能以及CYP1B1基因突变与POAG发病及进展关系的研究进展进行总结.     

Comparison of total/active ghrelin levels in primary open angle glaucoma, pseudoexfoliation glaucoma and pseudoexfoliation syndrome

AIM: To investigate the levels of ghrelin (Gh), acylated ghrelin (AGh) and AGh/Gh ratio in the humor aqueous (HA) of cases with pseudoexfoliation syndrome (PXS), pseudoexfoliation glaucoma (PXG), primary open angle glaucoma (POAG) and to compare these with control subjects. METHODS: A prospective examination was made of the total Gh, and AGh levels in HA of 67 patients undergoing cataract surgery. Patients were divided into 4 groups. HA samples were aspirated at the beginning of the surgery, stored at -70oC. Gh and AGh quantification was performed with ELISA kits and the AGh/total-Gh ratios were calculated. ANOVA, Kruskal-Wallis, Chi-square and post-hoc tests were used for statistical analysis. RESULTS: Total Gh levels in HA were 189.2±45.6 pg/mL in the control group, 199.2±32.9 pg/mL in PXS, 180.6±20.9 pg/mL in PXG and 176.8±21.4 pg/mL in POAG groups (P>0.05). AGh levels in HA were 23.09±5.01 pg/mL in the control group, 24.13±5.22 pg/mL in PXS, 22.29±1.55 pg/mL in PXG and 19.69±2.93 pg/mL in POAG groups (P>0.05). The ratio of AGh/Gh was 10.3%±2.34% in the control group, 13.03%±2.58% in PXS, 12.3%±1.54% in PXG and 11.79%±1.41% in POAG groups (P=0.044). The difference between the PXS and control groups was significant (P=0.03). CONCLUSION: In spite of statistically insignificant results, the HA total Gh levels were lower than those of the control subjects but not parallel with the AGh levels in glaucoma patients. The relative increase in the AGh/Gh ratio in glaucoma cases supports the view that proportional increases of AGh might play a role in the pathogenesis of glaucoma.