Twenty Novel MicroRNAs in the Aqueous Humor of Pseudoexfoliation Glaucoma Patients.

The microRNAs (miRNAs) are short non-coding RNAs (19-25 nt) that regulate the level of gene expression at the post-transcriptional stage. Altered miRNAs expression can lead to the development of various diseases, e.g., pseudoexfoliation glaucoma (PEXG). In this study, we assessed the levels of miRNA expression in the aqueous humor of PEXG patients using the expression microarray method. Twenty new miRNA molecules have been selected as having the potential to be associated with the development or progression of PEXG. Ten miRNAs were downregulated in PEXG (hsa-miR-95-5p, hsa-miR-515-3p, hsa-mir-802, hsa-miR-1205, hsa-miR-3660, hsa-mir-3683, hsa -mir-3936, hsa-miR-4774-5p, hsa-miR-6509-3p, hsa-miR-7843-3p) and ten miRNAs were upregulated in PEXG (hsa-miR-202 -3p, hsa-miR-3622a-3p, hsa-mir-4329, hsa-miR-4524a-3p, hsa-miR-4655-5p, hsa-mir-6071, hsa-mir-6723-5p, hsa-miR-6847-5p, hsa-miR-8074, and hsa-miR-8083). Functional analysis and enrichment analysis showed that the mechanisms that can be regulated by these miRNAs are: extracellular matrix (ECM) imbalance, cell apoptosis (possibly retinal ganglion cells (RGCs)), autophagy, and elevated calcium cation levels. Nevertheless, the exact molecular basis of PEXG is unknown and further research is required on this topic.

Real-world outcomes of cisplatin, capecitabine, and gemcitabine with either epirubicin (PEXG) or docetaxel (PDXG) as first-line palliative treatment in metastatic or unresectable locally advanced pancreatic adenocarcinoma.

BACKGROUND: First-line palliative chemotherapy regimens in advanced pancreatic adenocarcinoma include triplet chemotherapy with 5-fluorouracil, oxaliplatin, and irinotecan, and the doublet of nab-paclitaxel plus gemcitabine. Use of triplet chemotherapy in real-world populations is limited by tolerability and nab-paclitaxel is not universally available. Regimens using the combination of cisplatin, capecitabine, gemcitabine, and either epirubicin or docetaxel may be better tolerated, more widely available, and similarly effective, but no published real-world data exist. METHODS: A retrospective cohort review of patients with metastatic or unresectable locally advanced pancreatic adenocarcinoma treated with first-line palliative cisplatin, capecitabine, gemcitabine, and either epirubicin or docetaxel chemotherapy at Auckland City Hospital between July 1, 2013 and July 30, 2020. The primary outcome was overall survival (OS). Secondary outcomes were rates of grade 3 or 4 hematological toxicity, rate of febrile neutropenia, number of cycles received, and reasons for discontinuation. RESULTS: Eighty-eight patients were included. Median age was 66 years (range 39-79), 28.4% had unresectable, locally advanced disease and 71.6% metastatic disease. Median OS was 8.5 months. Patients stopped treatment due to disease progression (53.4%), completing 12 cycles (19.3%), or toxicity (10.2%). Grade 4 neutropenia was experienced by 21.6%; 10.2% had febrile neutropenia. There were four treatment-related deaths. CONCLUSION: This retrospective study in a real-world population demonstrates that chemotherapy with cisplatin, capecitabine, and gemcitabine with epirubicin (PEXG) or docetaxel (PDXG) had similar effectiveness to more commonly used combination regimens. PDXG/PEXG are viable alternatives to nab-paclitaxel plus gemcitabine in countries that have restricted drug funding.

Small Nucleolar RNAs in Pseudoexfoliation Glaucoma.

Small nucleolar RNAs (snoRNAs) are small non-coding regulatory RNAs that have been investigated extensively in recent years. However, the relationship between snoRNA and glaucoma is still unknown. This study aims to analyze the levels of snoRNA expression in the aqueous humor (AH) of patients with pseudoexfoliation glaucoma (PEXG) compared to a control group and identify hypothetical snoRNA-dependent mechanisms contributing to PEXG. The AH was obtained from eighteen Caucasian patients, comprising nine PEXG and nine age-matched control patients. RNA was isolated, and a microarray system was used to determine the snoRNA expression profiles. Functional and enrichment analyses were performed. We identified seven snoRNAs, SNORD73B, SNORD58A, SNORD56, SNORA77, SNORA72, SNORA64, and SNORA32, in the AH of the PEXG and control group patients. Five snoRNAs showed statistically significantly lower expression in the PEXG group, and two snoRNAs had statistically significantly higher expression in the PEXG group compared to the control group. In addition, we identified two factors-CACNB3 for SNORA64 and TMEM63C for SNORA32, similar to PEX-related genes (CACNA1A and TMEM136). The enrichment analysis for four genes targeted by snoRNAs revealed possible mechanisms associated with glaucoma and/or PEX, but the direct role of snoRNAs in these biological processes was not proven.

Canaloplasty in Pseudoexfoliation Glaucoma. Can It Still Be Considered a Good Choice?

Purpose: The aim of this study was to assess the long-term outcomes of canaloplasty surgery in pseudoexfoliation glaucoma (PEXG) patients. Material and Methods: A total of 116 PEXG patients with an intraocular pressure (IOP) > 21 mm/Hg and maximum tolerated local medical therapy who underwent canaloplasty from February 2008 to January 2022 were considered. Every six months, all subjects underwent a complete ophthalmic examination. The period of follow-up ranged from 2 to 167 months. Inclusion criteria included only patients for whom the entire procedure could be completed with a follow-up of at least 2 years. Results: Amongst the 116 PEXG patients, the entire procedure could not be performed in 10 eyes (8.6%), and thus they were not considered in the analysis. Twenty-three patients did not reach the two-year follow-up and another 16 patients during this time period were lost. A total of 67 patients with a mean follow-up of 49 ± 32.3 months were considered in the analysis. The pre-operative mean IOP was 31.2 ± 8.7 mm/Hg (range 20−60). The mean IOP at the two-year follow-up was 17.2 ± 6.7 mmHg, with a mean reduction from baseline of 44.9%. After two years, the qualified success rates according to three different criteria (IOP ≤ 21, ≤18 and ≤16 mmHg) were 80.6%, 73.1% and 61.0%, respectively. The total number of medications used pre- and at the follow-up at 2 years was 3.5 ± 0.8 and 1.2 ± 1.4, respectively. Early complications included: hyphema, in about 30% of cases; Descemet membrane detachment (4.9%); and IOP spikes > 10 mmHg (9.7%). A late failure with an acute IOP rise of up to 50 mmHg was observed in 41 cases (61.2%) after 3 to 72 months. Conclusions: Long-term post-operative outcomes of canaloplasty in PEXG patients appear to be quite good on average; however, an acute rise in IOP can be observed in more than 60% of the cases after a long period of satisfactory IOP control. For this reason, canaloplasty may not be suitable in eyes with PEXG, especially in patients with severe functional damage.

MicroRNAs in the aqueous humor of patients with different types of glaucoma.

PURPOSE: The aim of the study was to compare the frequency and the level of expression of selected miRNAs in the aqueous humor of patients with various types of glaucoma. METHODS: The studied group consisted of 42 patients with glaucoma: 19 with primary open-angle glaucoma (POAG), 14 with pseudoexfoliation glaucoma (PEXG), 9 with primary angle closure glaucoma (PACG), and the control group of 36 patients with senile cataract without glaucoma. The real-time polymerase chain reaction method was used to analyze the expression of miRNAs. RESULTS: There were no significant differences in the frequency and the level of miRNA expression between various types of glaucoma. There was a tendency for hsa-miR-6722-3p and hsa-miR-184 to be expressed more frequently in PEXG and hsa-miR-1260b in POAG. The expression levels of hsa-miR-1260b and hsa-miR-6515-3p were correlated with age in POAG. Target annotation and functional analyses showed that genes targeted by the most frequently expressed miRNAs (hsa-miR-1202, -1260b, -184, -187-5p, -6515-3p, -6722-3p, and hsa-mir-4634) are involved mainly in response to hypoxia, cardiovascular system development, and apoptosis. CONCLUSION: Hsa-miR-1260b was the most abundantly expressed among studied miRNAs and may be a potential biomarker of clinical status in PEXG and PACG.

Combined and stand-alone XEN 45 gel stent implantation: 3-year outcomes and success predictors.

PURPOSE: To evaluate the 3-year treatment outcomes of XEN 45 gel stent in open-angle glaucoma patients. METHODS: In this prospective, single-centre interventional study, consecutive eyes with uncontrolled intraocular pressure (IOP) or signs of disease progression despite medical treatment underwent XEN implantation either alone or combined with phacoemulsification (Phaco + XEN). MAIN OUTCOME MEASURES: Surgical success was defined as 'complete' when 36-month unmedicated IOP was ≤15 mmHg with a relative IOP reduction ≥ 20% from medicated baseline, while the definition of qualified success allowed no more medications than at baseline. Other definitions of success with different IOP thresholds were also analysed. Secondary outcomes included mean IOP reduction, changes in ocular hypotensive medications and rates of reoperations. RESULTS: Out of 149 eyes initially included, 92 eyes (61.7%) of 68 patients had complete 3-year data (XEN: n = 26; Phaco + XEN: n = 66) after 38.2% were lost to follow-up. Mean age was 76.3 ± 9.1 years, and 66.2% were female. Mean medicated IOP decreased from 20.8 ± 7.4 mmHg (21.0 ± 7.4 [XEN] vs. 20.0 ± 6.9 mmHg [Phaco + XEN]) at baseline to 13.1 ± 3.4 mmHg (12.9 ± 2.9 [XEN] vs. 12.9 ± 3.4 [Phaco + XEN]) at 3 years (-37.0%; p < 0.001). Medications decreased from 1.9 ± 1.3 (2.4 ± 1.5 [XEN] vs. 1.9 ± 1.2 [Phaco + XEN]) to 0.4 ± 0.9 (0.3 ± 0.8 [XEN] vs. 0.5 ± 0.9 [Phaco + XEN]) (-78.9%; p < 0.001). Complete success and qualified success were achieved in 29.0% and 31.0% of eyes, respectively. Needling revision was performed in 51 eyes (55.4%), and 26.1% underwent reoperations. Risk factors for surgical failure included male gender (odds ratio [OR]:3.6; p = 0.03), diagnosis of POAG (OR: 4.5; p < 0.01) and undergoing needling revision (OR: 4.6; p < 0.01). While the type of procedure had no effect on the outcomes of PEXG, POAG eyes undergoing combined surgery had significantly higher rates of failure (OR: 7.29; p = 0.023). Most patients stable at 12-month remained so through to 3 years. CONCLUSIONS: At 3 years, XEN gel stent implantation achieved clinically significant IOP and medication reduction despite relatively high rates of needling and reoperations. Identifying patients at risk preoperatively may help optimize surgical outcomes.

Association of IL-10 gene promoter polymorphisms with susceptibility to pseudoexfoliation syndrome, pseudoexfoliative and primary open-angle glaucoma.

BACKGROUND: The involvement of cytokines in pathogenesis of pseudoexfoliation syndrome and glaucoma has been demonstrated in several studies. The aim of the present study was to explore the association between three promoter polymorphisms -592C/A (rs1800872), - 819C/T (rs1800871) and -1082A/G (rs1800896) of interleukin 10 (IL-10) gene with susceptibility to pseudoexfoliation syndrome (PEX), pseudoexfoliative glaucoma (PEXG), and primary open-angle glaucoma (POAG). METHODS: In this study, 114 PEX, 118 PEXG, 114 POAG patients and 126 healthy individuals from Iranian population were participated. Detailed ophthalmic examinations by an ophthalmologist including slit-lamp bio-microscopic examination, dilated examination of the lens, gonioscopy, and funduscopy were carried out on patients and controls. Genomic DNA was extracted from the blood samples and ARMS-PCR was performed to detect promoter polymorphisms of IL-10. RESULTS: In all three SNPs studied, there was a significant difference in the genotype distribution between patients and control subjects. Results revealed that the AA genotype of IL-10 -592C/A SNP is associated with PEX. However, TT genotype of -819C/T and AA genotype of -1082A/G SNP are significantly associated with susceptibility to either PEX or PEXG and POAG disorders. Furthermore, the ACC haplotype containing the IL-10 -1082A allele was associated with PEX (P = 0.02, OR = 5.76, 95% CI = 5.17-24.49), PEXG (P = 0.006, OR = 7.54, 95% CI = 6.62-30.76) and POAG (P = 0.003, OR = 8.11, 95% CI = 7.13-33.15). CONCLUSIONS: Our results demonstrated that IL-10 gene promoter polymorphisms are associated with susceptibility to PEX, PEXG and POAG in Iranian population. Considering the fact that IL-10 polymorphisms are associated with various IL-10 expressions, further research is needed to explain its involvement in these disorders and the formation of extracellular fibrillar amyloid deposits in PEX and PEXG.

Evaluation of the anterior chamber angle in pseudoexfoliation syndrome.

BACKGROUND: Pseudoexfoliation syndrome (PEX) is the most frequently identifiable cause of secondary open-angle glaucoma, known as pseudoexfoliation glaucoma. The exact pathophysiology and etiology of PEX and associated glaucoma remains obscure. OBJECTIVES: The purpose of this study was to determine the differences in the morphology of the anterior chamber angle in people with pseudoexfoliation syndrome and pseudoexfoliation glaucoma compared to a control group. We also evaluated the correlation between intraocular pressure (IOP) and pigmentation of the angle with the amount of exfoliated material in the anterior segment. MATERIAL AND METHODS: The study group was composed of 155 eyes from 103 patients aged between 43 and 86 years. Each patient underwent a complete ophthalmological examination. RESULTS: Some difference was found in intraocular pressure between the PEX group and the control group and between the pseudoexfoliation glaucoma group and the control group, but no significant difference was found between the 2 study groups. There was a significant difference in the incidence of some degree of pigmentation in the anterior chamber angle and no difference in the widths of the angle between each group. A significant positive relationship was observed between intraocular pressure and the degree of pigmentation of the anterior chamber angle in both the PEX group and the pseudoexfoliation glaucoma group. CONCLUSIONS: The results of this study indicate that the amount of pigmentation and exfoliation material in the anterior segment significantly correlates with the level of IOP and possibly with the degree of trabecular dysfunction. It seems that for clear identification of PEX and pseudoexfoliation glaucoma factors, clinical assessment appears to be insufficient.