Identification of potential core genes in pseudoexfoliation using bioinformatics analysis and retrospective analysis of 84 patients with this disease.

BACKGROUND: Pseudoexfoliation (XFS) is a common cause of glaucoma in nowadays. Because of XFS causing irreversible blindness secondary to glaucoma (XFG), this study aims to identify the current prevalence of XFS among Xinjiang Province of China, and identify the hub genes involved in XFS. METHODS: A retrospective chart review was conducted from 2007 to 2019 for patients aged 50 and older. All patients with XFS or XFG diagnosed by slit lamp exam were identified through chart review. RESULTS: Of the 84 patient charts available for review, 50% of the patients identified as male, with a mean age of 67 years. The top ten genes evaluated by connectivity degree in the PPI network were identified. The results showed that Tyrobp was the most outstanding gene, followed by Ptprc, Fcgr3, Itgb2, Emr1, Cd68, Syk, Fcerlg, Hck, and Lyz2. All of these hub genes were downregulated in XFS. CONCLUSION: Our findings show a considerably biomarkers of XFS for diagnosis and treatment.

Evaluation of lamina cribrosa parameters, nerve fiber thickness, and macular thickness in primary open-angle glaucoma and pseudoexfoliation glaucoma using optical coherence tomography.

PURPOSE: To evaluate the lamina cribrosa, retinal nerve fiber layer (RNFL), and macula in patients with primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (PEXG) and healthy individuals using enhanced depth imaging (EDI) of spectral-domain optical coherence tomography (SD-OCT). METHODS: A total of 158 eyes were included in the study, comprising 58 eyes of 29 patients with POAG, 50 eyes of 25 patients with PEXG, and 50 eyes of 25 healthy individuals. The lamina cribrosa thickness (LCT) (at three locations), lamina cribrosa depth (LCD), RNFL thickness, and the macular thickness were measured using the EDI mode of the SD-OCT. The results were compared among the three groups. RESULTS: In both POAG and PEXG groups, the LCT was significantly thinner in the center, mid-superior, and mid-inferior areas in both eyes than in the control group (p < 0.001). However, no statistically significant difference was observed between the POAG and PEXG groups in terms of LCT at all three measurement locations in both eyes (p > 0.05). The LCD was significantly lower in the control group compared to the POAG and PEXG groups (p < 0.05), but there was no significant difference between the POAG and PEXG groups (p > 0.05). The RNFL thickness was significantly lower in both the POAG and PEXG groups compared to the control group in both eyes (p < 0.05). CONCLUSION: The LCT and LCD of patients with POAG and PEXG were thinner than those of healthy individuals, but there was no significant difference between the patients with POAG and PEXG.

Critical role of transcriptome-wide m6A methylation in the aqueous humor of patients with pseudoexfoliation glaucoma.

N6-methyladenosine (m6A) modification is one of the most common types of methylation modifications in eukaryotic mRNA. However, its role in the pathogenesis of pseudoexfoliation glaucoma (PXG) has not yet been reported. To enhance understanding in this regard, we assessed the m6A methylome in the aqueous humor of patients with PXG. MeRIP-Seq and RNA-Seq analyses were performed to compare the m6A methylomes and gene expression profiles of the aqueous humor of patients with PXG with those of patients with age-related cataract (ARC). Colorimetric m6A quantification was performed to detect global m6A levels. Quantitative reverse transcription PCR confirmed the expression of m6A-related enzymes and mRNAs in both groups. Results showed significantly higher aqueous humor m6A levels in the PXG group than in the ARC group. Five m6A-related enzymes, including METTL3, YTHDC2, HNRNPA2B1, HNRNPC, and LRPPRC, were significantly up-regulated in PXG specimens. We also observed 9728 m6A-modified peaks related to 6126 gene transcripts in the PXG group, with more than 250 genes containing one m6A peak (hypomethylated or hypermethylated). The distribution of the m6A peaks was enriched in coding sequences and 3'-untranslated regions for both groups. GGAC motif structures were also significantly enriched. Bioinformatics analysis further revealed that m6A plays a critical role in extracellular matrix formation and histone deacetylation. Additionally, MMP14, ADAMTSL1, FN1, and HDAC1 showed significant changes in m6A methylation and mRNA expression in the PXG group. Therefore, m6A methylation may regulate extracellular matrix composition in PXG and METTL3 may be a pivotal regulator of this process. In the future, it would be necessary to investigate MMP14, ADAMTSL1, FN1, and HDAC1, which are potential target genes.

Uneventful Phacoemulsification after Trabeculectomy in Pseudoexfoliation Glaucoma versus Primary Open-Angle Glaucoma.

INTRODUCTION: Conflicting results have been reported on phacoemulsification in the filtered eyes with open-angle glaucoma. In this study, we aim to compare the effect of phacoemulsification after trabeculectomy between pseudoexfoliation glaucoma (XFG) and primary open-angle glaucoma (POAG). METHODS: Consecutive patients with XFG and POAG who underwent uneventful phacoemulsification after trabeculectomy with 5-fluorouracil (TRAB-PHACO group) were reviewed retrospectively and matched to patients who underwent trabeculectomy only (TRAB group). Comparisons were performed for IOP, medication numbers, and success rates. Surgical failure was defined as IOP >21 mm Hg or IOP ≤21 mm Hg with additional medication or glaucoma surgery. Survival analysis was investigated by Kaplan-Meier test and the factors influencing final success by multivariate logistic regression analysis. RESULTS: The records of 204 patients were reviewed. In XFG, when compared with the baseline, increase in IOP became statistically significant at the at 24-month visit in the TRAB-PHACO group (p = 0.002), at the 6-month visit (p = 0.001) in the TRAB group and remained so throughout the follow-up. In the TRAB-PHACO group, increase of glaucoma medications was statistically significant only at the last visit (p = 0.001) in XFG, at the 6-month visit (p = 0.02) in POAG and remained so throughout the follow-up. Two glaucoma types did not differ statistically from one another in terms of survival analysis. In the TRAB group, the additional glaucoma surgery was more common in XFG compared to POAG (p = 0.02). The trabeculectomy failure after phacoemulsification was related with an IOP spike >25 mm Hg at postoperative first 24h (p = 0.04). CONCLUSIONS: In the filtered eyes with XFG, uneventful phacoemulsification may delay time-related worsening in IOP control and may decrease the additional glaucoma surgery need.

Homeostatic alterations related to total antioxidant capacity, elemental concentrations and isotopic compositions in aqueous humor of glaucoma patients.

Glaucoma is a multifactorial eye disease, characterized by progressive optic neurodegeneration. Elevation of the intraocular pressure is the main risk factor for glaucoma and is a consequence of an imbalance in the aqueous humor hydrodynamics, the physiology of which is influenced by the homeostatic equilibrium of essential elements, oxidative stress, and antioxidants. The aim of this work was to study local alterations in glaucomatous patients from two different, but connected, points of view: (i) the total antioxidant capacity (as an indicator of oxidative damage) and (ii) the concentration of mineral elements and their isotopic composition. Such objective was pursued using aqueous humor from patients diagnosed with pseudoexfoliation glaucoma (PEXG, n = 17) and primary open-angle glaucoma (POAG, n = 5) and age-matched control subjects (n = 16). The total antioxidant capacity (TAC) was examined in both aqueous humor and 60 serum samples (n = 20 controls, n = 20 for PEXG, and n = 20 for POAG), both showing higher TAC for the glaucoma population. The concentrations of the essential mineral elements (Cu, Fe, Mg, Na, P, and Zn) and the isotopic compositions of Cu and Zn were determined in aqueous humor using single-collector and multi-collector inductively coupled plasma-mass spectrometry, respectively. Significant differences were established for Mg and P levels when comparing the results for glaucomatous patients with those for the control population (p < 0.01 and p < 0.05 for Mg and P respectively, ANOVA and Kruskal-Wallis). The Zn isotopic composition was significantly shifted from that for the control population for PEXG patients. A significant difference in the isotopic composition of Zn was also established between the PEXG and POAG glaucoma cohorts.

Macular, papillary and peripapillary perfusion densities measured with optical coherence tomography angiography in primary open angle glaucoma and pseudoexfoliation glaucoma.

PURPOSE: To compare the blood flow situation in primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (PXG) using optical coherence tomography angiography (OCTA). METHODS: In this prospective study a total of 26 POAG and 23 PXG eyes were included. All patients underwent a complete ophthalmological examination including standard automated perimetry, stereoscopic photographs of the optic disc, peripapillary retinal nerve fibre layer analysis and examination of vascular parameters of the optic nerve head (ONH), the peripapillary region and macula using OCTA. In addition to the vascular parameters recorded by the device, the vascular images were graphically evaluated using Image J. All recorded vascular parameters were compared between both groups and correlated to structural and functional parameters. RESULTS: The mean superficial perifoveal plexus perfusion density (PD) was significantly lower in PXG eyes than compared to POAG eyes using OCTA (32.57% ± 3.57% vs. 34.92% ± 2.11%, p = 0.007). The mean PD parameters for the superficial peripapillary plexus (40.98% ± 3.04% vs. 42.09% ± 2.29%, p = 0.152) as well as the size of the foveal avascular zone (FAZ) (0.23 mm2 ± 0.1 mm2 vs. 0.23 mm2 ± 0.09 mm2) did not differ between both groups. Additional graphic evaluation using Image J showed no significant difference for superficial perifoveal plexus PD (32.97% ± 1.11% vs. 33.35% ± 0.95%, p = 0.194) and peripapillary plexus PD (46.65% ± 0.83% vs. 46.95% ± 0.5%, p = 0.127) between the groups. Retinal nerve fibre layer (RNFL) thickness correlated significantly with peripapillary plexus PD for both OCTA data and Image J data (p < 0.001, p = 0.032). CONCLUSION: The severity of the glaucoma seems to be crucial for peripapillary and macular perfusion densities, and not the form of glaucoma. An additional graphic evaluation is a possible step that could be implemented to improve the comparability of OCTA scans and to optimize the possibility of quantitative perfusion analysis in the case of deviating quality criteria.

Long-term results of micropulse laser trabeculoplasty with 577-nm yellow wavelength in patients with uncontrolled primary open-angle glaucoma and pseudoexfoliation glaucoma.

Our aim was to evaluate the long-term results of micropulse laser trabeculoplasty (MLT) with 577-nm yellow wavelength in the treatment of glaucoma. We reviewed the medical records of 51 patients (51 eyes) with uncontrolled primary open-angle glaucoma or pseudoexfoliation glaucoma who underwent 180° MLT for the first time. The success of MLT was defined as an IOP reduction of ≥ 20% and IOP < 21 mmHg after treatment. If the number of medications was increased or further laser trabeculoplasty or glaucoma surgery was required after treatment, the case was considered unsuccessful. The mean duration of patient follow-up was 18.39 ± 12.17 months (range 3-52 months). Patients included in the study used 2-4 types of antiglaucoma eye drops (mean 3.43 ± 0.7). The mean number of MLT spots was 65.54 ± 6.19, and the mean energy level was 750.98 ± 101.73 mJ. The decrease in intraocular pressure compared to baseline measurements was: 16.72 ± 11.87%, 15.07 ± 13.76%, 12.63 ± 14.29%, 16.66 ± 19.32%, and 16.75 ± 19.78% during follow-up at 3, 6, 12, 24, and 36-48 months. Successful response was achieved in 35.41%, 36.95%, 34.21%, 40%, 41.17%, and 42.85% of patients during 3, 6, 12, 18, 24, and 36-48 months of follow-ups, respectively. Of the 51 eyes studied, 12 patients (23.5%) underwent post-MLT glaucoma surgery, and 7 patients (13.7%) had cataract surgery, whose follow-up data were subsequently censored. The reduction of intraocular pressure showed a significant correlation with baseline intraocular pressure, while age and laser power showed no correlation (p > 0.05). MLT is a novel treatment option for patients with glaucoma with favorable long-term outcomes and a good safety profile.

Dysregulated Retinoic Acid Signaling in the Pathogenesis of Pseudoexfoliation Syndrome.

Pseudoexfoliation (PEX) syndrome, a stress-induced fibrotic matrix process, is the most common recognizable cause of open-angle glaucoma worldwide. The recent identification of PEX-associated gene variants uncovered the vitamin A metabolic pathway as a factor influencing the risk of disease. In this study, we analyzed the role of the retinoic acid (RA) signaling pathway in the PEX-associated matrix metabolism and evaluated its targeting as a potential candidate for an anti-fibrotic intervention. We provided evidence that decreased expression levels of RA pathway components and diminished RA signaling activity occur in an antagonistic crosstalk with TGF-ß1/Smad signaling in ocular tissues and cells from PEX patients when compared with age-matched controls. Genetic and pharmacologic modes of RA pathway inhibition induced the expression and production of PEX-associated matrix components by disease-relevant cell culture models in vitro. Conversely, RA signaling pathway activation by natural and synthetic retinoids was able to suppress PEX-associated matrix production and formation of microfibrillar networks via antagonization of Smad-dependent TGF-ß1 signaling. The findings indicate that deficient RA signaling in conjunction with hyperactivated TGF-ß1/Smad signaling is a driver of PEX-associated fibrosis, and that restoration of RA signaling may be a promising strategy for anti-fibrotic intervention in patients with PEX syndrome and glaucoma.

The effect of uneventful cataract surgery in pseudoexfoliation glaucoma with or without previous mitomycin C-augmented trabeculectomy.

PURPOSE: To analyze the effect of uneventful cataract surgery on intraocular pressure (IOP) in pseudoexfoliation glaucoma (PXG) eyes with and without a history of Mitomycin C-augmented trabeculectomy. METHODS: Eyes with PXG that had underwent uneventful cataract surgery were enrolled. The IOP and the medication numbers before cataract surgery, and 1, 3, 6, 12, 18, 24 months after cataract surgery, and at the last visit were recorded in PXG with and without previous trabeculectomy. Failure was defined as IOP > 21 or ≤ 21 mmHg with additional medication or surgery. In the postoperative first 24 h, IOP > 50% above baseline was defined as an IOP spike. RESULTS: In the trabeculectomized eyes (n = 37), the increase in the mean IOP (p = 0.024) and the increase in the mean number of medications (p = 0.007) was significant at the last visit when compared with baseline. In the non-trabeculectomized eyes (n = 42) there was a significant decrease in the mean IOP (p = 0.016) and in the mean number of medications (p = 0.038) at the last visit. Twelve eyes (32.4%) in trabeculectomized group and six (14.3%) in the non-trabeculectomized group experienced failure. An IOP spike was seen in one eye in the trabeculectomized group, in 15 eyes in the non-trabeculectomized group (p < 0.0001). The IOP spike was a significant risk factor for failure (p = 0.027). CONCLUSION: Uneventful cataract surgery may have significant negative effect on the IOP control in the trabeculectomized PXG eyes. After cataract surgery, the non-trabeculectomized PXG eyes had a higher risk of IOP spike and an IOP spike may be a risk factor for failure.

Comparison of long-term results of trabeculectomy and phacotrabeculectomy in patients with pseudoexfoliation glaucoma and primary open-angle glaucoma: a single-center study.

PURPOSE: To evaluate long-term surgical success and complications in pseudoexfoliation glaucoma (PEXG) and primary open-angle glaucoma (POAG) after trabeculectomy or phacotrabeculectomy. METHODS: 96 PEXG eyes and 114 POAG eyes who underwent primary trabeculectomy and phacotrabeculectomy were retrospectively evaluated considering intraocular pressure (IOP), the number of glaucoma medications, surgical success, and rate of complications. Two success criteria were used: Complete success comprised IOP of 5-18 mmHg and 20% reduction of baseline IOP without medication. Qualified success comprised IOP of 5-18 mmHg and 20% reduction of baseline IOP irrespective of medication. Success rates in PEXG and POAG groups, trabeculectomy and phacotrabeculectomy groups, and four groups divided according to surgery and etiology were analyzed via Kaplan-Meier survival analysis. RESULTS: The complete and qualified success were not different between PEXG and POAG groups. The qualified success curves show a similar pattern among the four groups throughout the follow-up of 1,2,3,5,7 and 9 years. Baseline IOP and the number of medications were similar in all four groups (p = 0.275 and p = 0.209, respectively). IOP levels and the number of medications were not statistically different between the four groups during the follow-up of 2,5 and 7 years. The total number of complications and interventions were similar between PEXG and POAG groups (p = 0.258). CONCLUSIONS: Phacotrabeculectomy is an effective procedure as trabeculectomy with similar surgical success rates and few surgical complications when it comes to treating PAOG and PEXG patients. Both approaches resulted in similar postoperative IOP levels and medication numbers in both groups.

A comprehensive enhanced depth imaging spectral-domain optical coherence tomography analysis of pseudoexfoliation spectrum from non-glaucomatous to advanced stage glaucoma in the aspect of Bruch's membrane opening-minimum rim width.

PURPOSE: To compare the correlations between lamina cribrosa (LC) and related structures with Bruch's membrane opening-minimum rim width (BMO-MRW) and retinal nerve fiber layer (RNFL) thickness in pseudoexfoliation syndrome (PXS) and different stages of pseudoexfoliation glaucoma (PXG). METHODS: This prospective cross-sectional study included 32 PXS eyes of 24 patients and 94 PXG eyes (early-stage (n: 55) and advanced-stage glaucoma (n: 39) of 78 patients. Global and six sectors of RNFL thicknesses and BMO-MRW parameters were measured with enhanced depth imaging (EDI) mode of SD-OCT. Structural parameters; lamina cribrosa thickness (LCT), lamina cribrosa depth (LCD), prelaminar tissue thickness (PLTT), four quadrants of peripapillary choroidal thicknesses (PPCT), and subfoveal choroidal thickness (SFCT) were measured and statistical relationships between the structural parameters have been laid out. We apply the generalized estimating equations method to take into account dependency of right and left eyes. RESULTS: From PXS to mild and advanced PXG groups LCT and PLTT decrease from 147.29 ± 33.10, 145.62 ± 30.64, 126.30 ± 29.14 and 260.93 ± 185.07, 247.27 ± 142.58, 159.89 ± 86.84, respectively, and LCD varies as 159.89 ± 86.84, 420.88 ± 117.80, and 505.64 ± 183.25. The correlations between LCD, LCT, and PLTT and the stage of the disease are significant. BMO-MRW shows slightly stronger correlations than the RNFL with LC related parameters. SFCT does not exhibit any significant relationship with the stage of the disease. However, PPCT in only the interior quadrant does. The significant correlations between LCD and all quadrants of PPCT is the sign of important anatomic relationship. CONCLUSION: These findings show that the BMO-MRW parameter may be more sensitive than RNFL and can safely be used in the diagnosis and follow-up in PXS and PXG, but this result should be supported with longer and larger series.

Evaluation of aqueous humor and serum clusterin levels in patients with glaucoma.

BACKGROUND: To compare the aqueous humor (AH) and the serum clusterin levels of patients with pseudoexfoliation syndrome (PEX), pseudoexfoliation glaucoma (PEXG), and primary open-angle glaucoma (POAG) with each other and with an age- and sex-matched control group. METHODS: This prospective, cross-sectionalstudy evaluated 92 eyes from 92 adult cases of uncomplicated phacoemulsification and posterior chamber intraocular lens (IOL) implantation. The cases were divided into PEX, PEXG, POAG, and control groups. Serum samples were taken from the antecubital vein just before the surgery, and the AH samples were aspirated at the beginning of the surgery. Kruskal-Wallis H, One-way ANOVA, Mann-Whitney U with Bonferroni correction and Chi-Square tests were used for statistical analysis. RESULTS: The serum clusterin levels were the highest in the PEXG group, but no statistically significant differences were observed between the groups (p=0.633). The mean AH clusterin levels were 286.79±29.64 µg/mL in the PEXG group, 263.92±31.70 µg/mL in the PEX group, 272.59±49.71 µg/mL in the POAG group, and 193.50±62.38 µg/mL in the control group (p< 0.001). This came out to be 1.48 times increase for the PEXG group, 1.36 for the PEX group, and 1.41 for the POAG group when compared with the control subjects. CONCLUSIONS: A higher level of clusterin in the anterior chamber was found to be associated with PEX and PEXG. In addition, a high level of anterior chamber clusterin in POAG, which is a new finding, showed that this molecule might be important not only in pseudoexfoliation, but also other types of glaucoma like POAG.

Results of fluorouracil-augmented Xen45 implantation in primary open-angle and pseudoexfoliation glaucoma.

PURPOSE: To report the effectiveness and safety of 5-fluorouracil (5-FU)-augmented Xen45 implantation in primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (PEXG). METHODS: This single-center, retrospective chart review study included 29 eyes that underwent 5-FU-augmented Xen45 implantation. Main outcome measures were intraocular pressure (IOP) levels and number of glaucoma medications. Surgical success was defined as IOP ≤ 21 mmHg and ≥ 20% reduction from preoperative levels without (complete success) or with (qualified success) glaucoma medications and without further glaucoma surgery at last follow-up. All postoperative interventions and complications were also noted. RESULTS: The mean age of the patients was 67.5 ± 10.3 years, and the mean follow-up time was 23.2 ± 12.6 months. Mean IOP was 24.5 ± 8.7 mmHg and decreased by 30.2% at 12 months, 24.9% at 24 months, and 31.7% at final visit (p < 0.001, p = 0.006, p > 0.001, respectively). Mean number of glaucoma medications decreased from 2.83 preoperatively to 0.71 at 12 months, 0.87 at 24 months, and 0.86 at final visit (p < 0.001). At final visit, the complete success rate was 48.3%, qualified success rate was 69%, and 62.1% of the eyes were free of glaucoma medications. Needling was performed in 7 eyes (24%). Adverse events included choroidal detachment in 5 eyes, hyphema in 2 eyes, and endophthalmitis in 1 eye. CONCLUSION: 5-FU-augmented Xen45 implantation in POAG and PEXG patients provided safe and effective IOP lowering with significant reduction of glaucoma medications up to 3 years.

Examination of retinal vascular density changes via optical coherence tomography angiography in patients with glaucoma.

PURPOSE: The aim of this study was to investigate the changes in vessel density (VD) in glaucoma patients and to investigate the relationship between VD and structural parameters using optical coherence tomography angiography. METHODS: Our study included 25 primary open-angle glaucoma (POAG) patients, 25 pseudoexfoliation glaucoma (PXG) patients and 25 healthy individuals. All patients underwent 6 × 6 mm retinal angiography (upper limit: internal limitan membrane [ILM], lower limit: 10 µm inferior to inner plexiform layer) and 4.5 × 4.5 mm disk angiography (upper limit: ILM, lower limit: posterior border of the retinal nerve fiber layer [RNFL]) via an optical coherence tomography (OCT) system (AngioVue, Optovue). Measures of vascular density were as follows: total area VD (tVD), intrapapillary VD (iVD), peripapillary VD (pVD) and parafoveal VD (pfVD). In addition to performing comparisons, the correlations between pVD, retinal nerve fiber layer (RNFL) thickness and optic nerve head measurement results were investigated. RESULTS: A total of 75 individuals were included in our study. In the POAG and PXG groups, tVD and pVD values were significantly lower than the control group (median tVDs were: 45.4, 45.9, 50.0, and median pVDs were: 50.0, 50.3, 53.1, respectively) (confidence intervals were: - 9.8/- 1.1 for pVD and - 8.6/- 1.4 for tVD). Significantly lower pf-VD values were detected in the PXG group compared to the control group (p < 0.05). There were strong positive correlations between RNFL thickness and pVD in in glaucoma groups (p < 0.001). There was no correlation between pVD and disk area, intraocular pressure and age in glaucoma patients. Patients using beta-blockers had significantly lower tVD and pVD values compared to those who did not (p < 0.05). CONCLUSION: The low VD values in glaucomatous eyes and the strong correlations between that values and RNFL thickness demonstrate a relationship between structural parameters and vascular parameters.

Comparison of vessel density in macular and peripapillary regions between primary open-angle glaucoma and pseudoexfoliation glaucoma using OCTA.

PURPOSE: The aim of our study was to compare macular and peripapillary vessel density using optical coherence tomography angiography (OCTA) between eyes with primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (PXG). METHODS: Thirty-six POAG and 34 PXG eyes with similar visual field defect (no statistically significant difference between average mean deviation and pattern standard deviation scores) were included. Macular superficial vessel density (msVD) in the superficial macular layer and foveal avascular zone (FAZ) parameters were assessed with (6 × 6 mm) and peripapillary vessel density (ppVD) in the radial peripapillary capillary (RPC) with (4.5 × 4.5 mm) OCTA scans. Area under the receiver operating curve was used for assessing diagnostic capability. RESULTS: In PXG group, all msVD parameters had lesser values, and especially in parafoveal region, statistically significant decrease was shown (p = 0.008) in all subdivisions except nasal (p = 0.053). FAZ area was more larger in PXG [0.32(0.25-0.36)] than POAG [0.28(0.22-0.39)],(p = 0.944). FAZ density - 300 µm had statistically significant decrease in PXG (47.22 ± 6.92) according to POAG groups (50.63 ± 7.25) (p = 0.048). Most of RPC VD parameters had decreasing values in PXG group (p > 0.05). VDs and corresponding thicknesses had significant remarkable positive correlation in both macular and peripapillary regions. Significant remarkable negative correlations were observed between fovea VD and FAZ area, FAZ perimeter and between fovea thickness and FAZ area, FAZ perimeter. CONCLUSION: PXG eyes were found to have lesser values in terms of VD in the macular area, especially in the parafoveal and FD-300 regions, compared to POAG eyes which had similar functional and structural glaucomatous damage. Patients whose etiology was PXG and who seemed to have the same functional damage as those with POAG were actually found to have greater macular vascular damage. In addition, it was observed that macular vascular parameters correlated with peripapillary vascular parameters.

Macular pigment optical density change analysis in primary open-angle glaucoma and pseudoexfoliation glaucoma.

PURPOSE: We aimed to investigate whether macular pigment optical density (MPOD) has a diagnostic value by comparing MPOD and retinal nerve fiber layer (RNFL), ganglion cell layer++ (GCL++) of patients with primary open-angle glaucoma (POAG) and pseudoexfoliation (PEX) glaucoma and normal individuals. METHODS: We included in the study 54 eyes of 34 patients with diagnosis POAG, 40 eyes of 25 patients with PEX glaucoma and 40 eyes of 20 normal individuals. The MPOD measurements of the cases were performed in the MPOD mode of the fundus fluorescein angiography (Carl Zeiss Visucam Meditec, Germany) device while the pupils were in dilated status. RNFL and GCL++ measurements of all individuals included in the study were done by swept source optical coherence tomography (DRI Triton swept source optical coherence tomography; Topcon, Tokyo, Japan). Intraocular pressures of all three groups were measured by Applanation tonometer. The relationship between MPOD, RNFL and GCL++ values were examined. Patients with additional ophthalmic disease, intraocular surgery, history of chronic drug use, and smokers were excluded in the study. RESULTS: MPOD mean and MPOD max values were significantly higher in patients with PEX glaucoma than POAG and control group (p < 0.05). MPOD mean and MPOD max measurements were not different when compared to POAG patients and control group (p > 0.05). RNFL and GCL++ measurements were found significantly thinner in patients with POAG and PEX glaucoma compared to the control group (p < 0.001). There was no correlation between MPOD values and RNFL or GCL++. MPOD max values show a very high correlation with age in a statistically significant positive direction (r = 0.90, p < 0.001). The average age of PEX glaucoma group was higher than the control group (p = 0.006). There was no age difference between the PEX glaucoma group and the POAG group (p > 0.05). Also, there was no difference in age between POAG and control groups. In POAG and PEX glaucoma groups, mean intraocular pressure values are significantly higher than the control group. CONCLUSIONS: In our study, no MPOD change was observed in the POAG group, while a statistically significant increase in MPOD was found in the PEX glaucoma group. As a result of these findings, we think that PEX syndrome also affects the posterior segment. Well-organized, large, prospective, and randomized studies should be developed for preventive treatment to the negative effects of PEX syndrome on all eye tissues.

Differential Lysyl oxidase like 1 expression in pseudoexfoliation glaucoma is orchestrated via DNA methylation.

Pseudoexfoliation syndrome (PXF) is the most common cause of secondary open angle glaucoma worldwide. Single nucleotide polymorphisms (SNPs) in the gene Lysyl oxidase like 1 (LOXL1) are strongly associated with the development of pseudoexfoliation glaucoma (PXFG). However, these SNPs are also present in 50-80% of the general population, suggestive of other factors being involved in the pathogenesis of PXFG. In this study, we aimed to investigate the influence of epigenetic regulation, specifically DNA methylation, on LOXL1 expression in PXFG using human tenons fibroblasts (HTFs), aqueous humour and serum samples from donors with and without PXFG. LOXL1 expression in HTFs was measured by qPCR and Western Blotting and LOXL1 concentration in aqueous humour was determined by ELISA. Global DNA methylation levels were quantified using an ELISA for 5-methylcytosine. MeDIP assays assessed the methylation status of the LOXL1 promoter region. Expression of methylation-associated enzymes (DNMT1, DNMT3a and MeCP2) were determined by qPCR and inhibited by 0.3 µM 5-azacytidine (5-aza). Results showed that LOXL1 expression was significantly decreased in PXFG HTFs compared with Control HTFs at gene (Fold change 0.37 ± 0.05, P < 0.01) level and showed a decrease, when measured at the protein level (Fold change 0.65 ± 0.42, P = 0.22), however this was not found to be significant. LOXL1 concentration was increased in the aqueous of PXFG patients compared with Controls (2.76 ± 0.78 vs. 1.79 ± 0.33 ng/ml, P < 0.01). Increased global methylation (56.07% ± 4.87% vs. 32.39% ± 4.29%, P < 0.01) was observed in PXFG HTFs compared with Control HTFs, as was expression of methylation-associated enzymes (DNMT1 1.58 ± 0.30, P < 0.05, DNMT3a 1.89 ± 0.24, P < 0.05, MeCP2 1.63 ± 0.30, P < 0.01). Methylation-associated enzymes were also increased when measured at protein level (DNMT1 5.70 ± 2.64, P = 0.04, DNMT3a 1.79 ± 1.55, P = 0.42, MeCP2 1.64 ± 1.33, P = 0.45). LOXL1 promoter methylation was increased in patients with PXFG compared to Control patients in both blood (3.98 ± 2.24, 2.10 ± 1.29, P < 0.05) and HTF cells (37.31 ± 22.0, 8.66 ± 10.40, P < 0.01). Treatment of PXFG HTFs with in 5-azacytidine increased LOXL1 expression when compared with untreated PXFG HTFs (Fold change 2.26 ± 0.67, P < 0.05). These data demonstrate that LOXL1 expression is altered in PXFG via DNA methylation and that reversal of these epigenetic changes may represent future potential therapeutic targets in the management of PXFG.

Evaluation of silent information regulator T (SIRT) 1 and Forkhead Box O (FOXO) transcription factor 1 and 3a genes in glaucoma.

Analysis of the reactive oxygen species (ROS)-detoxifying biomarkers may elucidate the mitochondrial dysfunction in glaucoma pathogenesis. Therefore, we purposed to investigate the effects of ROS-detoxifying molecules including Silent Information Regulator T1 (SIRT1) and Forkhead Box O 1 (FOXO1) and 3a (FOXO3a) transcription factors in patients with glaucoma. Our analyses included 20 eyes from patients with primary open-angle glaucoma (POAG) and 20 eyes from patients with pseudoexfoliation glaucoma (PXG) who were scheduled for trabeculectomy. After extraction of total RNA from trabecular meshwork tissue, we compared the levels of SIRT1, FOXO1and FOXO3a genes in the oxidative pathway with the level of glyceraldehyde-3 phosphate dehydrogenase (GAPDH), the reference gene, using real-time polymerase chain reaction. Relative gene expression was calculated using the threshold cycle (2-ΔΔCT) method. We observed similarly reduced expression levels of SIRT1, FOXO1, and FOXO3a genes versus GAPDH among patient groups (p = 0.40; p = 0.56; p = 0.35, respectively). This is the first study to identify the role of SIRT1 and FOXOs in human TM with glaucoma. Relative expression levels of SIRT1, FOXO1, and FOXO3a genes versus a control gene (GAPDH) were decreased in POAG and PXG groups. Our results show that SIRT1and FOXOs (1-3a) deserve special attention in the pathogenesis of glaucoma.

Relationship between homocysteine levels, anterior chamber depth, and pseudoexfoliation glaucoma in patients with pseudoexfoliation.

PURPOSE: This study investigates the relationship between plasma homocysteine levels, anterior chamber depth (ACD), and pseudoexfoliation glaucoma (PEXG) in patients with pseudoexfoliation syndrome. METHODS: Sixty patients (F:M = 35:25) with pseudoexfoliation (PEX) were divided into two groups based on their plasma homocysteine levels; group 1 (< 20 µmol/L, normal) and group 2 (≥ 20 µmol/L, high). Intraocular pressure (IOP) and ACD values as well as plasma homocysteine levels were compared between the two groups. Moreover, the mean values for ACD and IOP were compared between patients stratified according to the reference upper limit for the homocysteine level (above and below 14 µmol/L), and the prevalence of high IOP was estimated. RESULTS: Groups 1 and 2 showed no statistically significant differences in the mean ACD (3.04 ± 0.28 vs. 3.07 ± 0.31 mm, respectively) and mean IOP (20.63 ± 10.22 vs. 21.67 ± 7.55 mmHg, respectively). Patients with PEX and homocysteine levels > 14 µmol/L had a significantly increased prevalence (P < 0.05) of high IOP (≥ 22 mmHg). CONCLUSIONS: Patients with PEX and high homocysteine levels have an increased prevalence of high IOP. No relationship exists between plasma homocysteine levels and ACD. Thus, PEXG should be suspected in patients with PEX and high plasma homocysteine levels. Plasma homocysteine levels could be helpful for the diagnosis of PEXG, although larger sample studies are required to confirm this finding.

[Glaucomatous visual field loss in eyes undergoing first trabeculectomy in Iceland]. / Sjónsviðsskerðing við fyrstu hjáveituaðgerð (trabeculectomiu) vegna gláku

INTRODUCTION: Glaucoma is a degenerative disease in the optic nerve with associated visual field defects (VFD). Trabeculectomy is the most common glaucoma surgery. Surgery is indicated if glaucomatous optic neuropathy progresses despite tolerated medical treatment or in patients with severe VFD. The purpose of this paper is to describe the severity of visual field damage in patients undergoing their first trabeculectomy in Iceland. METHODS: A retrospective review of medical records of all patients with open angle glaucoma that underwent first trabeculectomy at Landspítali University Hospital, from June 2013 to March 2016. Visual fields were examined by Octopus automated perimetry and the severity of glaucoma damage was staged according to the mean defect (MD). RESULTS: 86 eyes were included in the study, mean age 75 ± 11 years, 57% men. Patients used on average three IOP lowering medications. Mean MD at referral to surgery was 13.4 ± 7.7dB (min 0.8dB, max 26.2 dB), 21% had early glaucomatous damage (MD <6dB), 23% moderate (MD 6-12 dB) and 56% severe (MD > 12). CONCLUSION: VFD at referral to surgery varied from mild VFD to severe damage. Like clinical guidelines recommend, treatment seems to be individualized and the most common indication for surgery was increased VFD despite medical treatment. Mean MD at referral to surgery was high compared to other studies. Eyes with severe VFD had on average lower IOP and thinner cornea. This might indicate that great emphasis is placed on high IOP and perhaps too little emphasis on VFD and cornea thickness.