Purpose: To investigate the relationship between glaucoma, pseudoexfoliation and hearing loss (HL). Methods: A systematic literature search following PRISMA guidelines was conducted using the PubMed, Embase, Scopus and Cochrane databases from 1995 up to 28 August 2023. Results: Thirty studies out of the 520 records screened met the inclusion criteria and were included. Most articles (n = 20) analysed the association between pseudoexfoliation syndrome (XFS) and HL, showing XFS patients to have higher prevalence of sensorineural hearing loss (SNHL) at both speech frequencies (0.25, 0.5, 1 and 2 kHz), and higher frequencies (4 and 8 kHz) compared to controls in most cases. No significant differences in prevalence or level of HL between XFS and pseudoexfoliative glaucoma (XFG) were detected in most studies. Eight articles analysed the relationship between primary open-angle glaucoma (POAG) and HL. Overall, a positive association between the two conditions was highlighted across all studies except for two cases. Similarly, articles focusing on NTG and HL (n = 4) showed a positive association in most cases. The role of autoimmunity and, in particular, the presence of antiphosphatidylserine antibodies (APSA) in patients with NTG and HL suggested an underlying autoimmune or vascular mechanism contributing to their pathogenesis. Only one study analysed the relationship between angle-closure glaucoma (ACG) and HL, showing higher incidence of ACG in patients with SNHL compared to normal hearing controls. Conclusions: Most studies detected an association between XFS and HL as well as POAG/NTG/ACG and HL, suggesting the presence of a similar pathophysiology of neurodegeneration. However, given the strength of the association of XFS with HL, it remains unclear whether the presence of XFG is further associated with SNHL. Further research specifically targeted to assess the correlation between glaucoma, XFS and HL is warranted to provide a more comprehensive understanding of this association.

This systematic review summarizes evidence for associations between female reproductive factors (age at menarche, parity, oral contraceptive [OC] use, age at menopause, and postmenopausal hormone [PMH] use) and intraocular pressure (IOP) or open-angle glaucoma (OAG).
Understanding the associations between female reproductive factors and glaucoma may shed light on the disease pathogenesis and aid clinical prediction and personalized treatment strategies. Importantly, some factors are modifiable, which may lead to new therapies.
Two reviewers independently extracted articles in MEDLINE, Embase, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials databases to identify relevant studies. Eligibility criteria included studies with human subjects aged > 18 years; a measured outcome of either IOP or OAG; a cohort, case-control, cross-sectional, or randomized controlled trial design; a reported measure of association, such as the hazard ratio, relative risk, odds ratio, or mean difference, with an associated confidence interval; and a measured exposure of at least 1 of the following variables: age at menarche, parity, OC use, age at menopause, or PMH use.
We included a total of 27 studies. Substantial differences in study designs, exposure and treatment levels, treatment durations, and variable reporting precluded a meaningful quantitative synthesis of the identified studies. Overall, relatively consistent associations between PMH use and a lower IOP were identified. Estrogen-only PMH use may be associated with lower OAG risk, which may be modified by race. No significant associations were found with combined estrogen-and-progesterone PMH use. No strong associations between parity or age at menarche and glaucoma were found, but a younger age at menopause was associated with an increased glaucoma risk, and adverse associations were identified with a longer duration of OC use, though no overall association with OC use was found.
The association between PMH use and lower IOP or OAG risk is a potentially clinically relevant and modifiable risk factor and should be investigated further, although this needs to be interpreted in the context of a high risk of bias across included studies. Future research should examine associations with IOP specifically and how the relationship between genetic factors and OAG risks may be influenced by female reproductive factors.

OBJECTIVE: It had been reported that mutations in CYP1B1 gene probably play an important role in the pathogenesis of primary open angle glaucoma (POAG) but the existing genetic association studies show contradictory results. Thus, the objective of our study was to perform a systematic review and meta-analysis to characterize more precisely the potential association between given polymorphisms in CYP1B1 gene and the risk of suffering POAG.
METHODS: A systematic review of studies that related the risk of carrying CYP1B1 gene polymorphisms with POAG development was conducted. We selected 19 case-control studies including 3855 POAG patients and 4125 control subjects in our meta-analyses. A random effects model was used. Sensitivity analysis and assessment of bias were also included.
RESULTS: The prevalence of CYP1B1 gene polymorphisms were significantly more frequent among POAG patients compared to all controls (OR = 2.91, 95% CI = 1.37 - 6.21; P = 0.006). Moreover, their prevalence was significantly higher in juvenile-onset patients than in adult-onset ones (OR = 2.27, 95% CI = 1.20-4.28; P = 0.001).
CONCLUSIONS: The results of this meta-analysis uphold that being a carrier of polymorphic genetic variants in CYP1B1 gene would increase the risk of POAG, especially the juvenile onset.

BACKGROUND: Glaucoma is a progressive disease of the optic nerve that has several underlying causes, but in most cases, the cause is unknown. Given the importance of the role of nitric oxide in the occurrence of ocular nerve damage and the effect of eNOS gene polymorphic sites on protein function, to better understand the mechanism of formation of POAG, the relationship between polymorphisms rs2070744 and rs1799983 eNOS gene with POAG risk was investigated in this study using meta-analysis.
METHODS: In this study, systematic review and meta-analysis of study data related to the study of polymorphisms rs2070744 and rs1799983 eNOS gene in patients with POAG using the keywords eNOS, NOS3, Gluuc8898, POAG, primary open-angle glaucoma. It was extracted from SID, MagIran, IranMedex, IranDoc, ScienceDirect, Embase, Scopus, PubMed, Web of Science, and Google Scholar search engines without a time limit until May 2020. To perform the analysis of qualified studies, the model of random effects was used and the inconsistency of studies with the I2 index was investigated. Data analysis was performed with Comprehensive Meta-Analysis (Version 2).
RESULTS: In a review of 16 studies (9 studies on polymorphism rs2070744 and seven studies on polymorphism rs1799983) with a sample size of 1631 subjects and a control group of 2405 subjects related to polymorphism rs2070744 and a group of 1456 subjects and a control group of 2240 subjects related to polymorphism 9997 rs1, the odds ratio of TT, CT, and CC genotypes was reported to be 0.95, 1.01, and 1.14, respectively, and the odds ratio of GG, GT and TT genotypes to be 0.88, 0.97, and 1.31, respectively, was reported in patients with POAG.
CONCLUSIONS: The results of our systematic review and meta-analysis study show that the eNOS gene polymorphisms rs2070744 and rs1799983 may increase the risk of POAG among individuals. However, further studies are needed to confirm these findings.

Introduction: Glaucoma, a leading cause of irreversible blindness worldwide, is commonly diagnosed solely in advanced stages of the disease when important and irreversible losses of visual field have already occurred. The identification of effective biomarkers and methods for diagnostic purposes are main interests of the scientific community. Areas covered: This review presents an overview of the current diagnostic methods used for glaucoma and introduces the areas where new efforts are being done for the identification of more sensitive and specific biomarkers. The review then covers the patent literature of the period 2013-2019 regarding diagnostic approaches and biomarkers of glaucoma and the claimed methods for their qualitative and/or quantitative analysis. Expert opinion: In the absence of treatment, glaucoma can cause blindness in a few years. Early diagnostic tools are urgently needed, as this disease incidence is deemed to rapidly increase in the next decades. The current diagnosis of glaucoma, which is based on specific signs of the disease, such as high intraocular pressure, specific optic nerve head changes and visual field loss, is not enough anymore. Molecular genetics represents the area where most efforts are currently made to improve the early detection and monitoring of the disease progression.

Glaucoma is a leading cause of irreversible blindness worldwide. Primary open-angle glaucoma (POAG), the most common type, is a complex inherited disorder that is characterized by progressive retinal ganglion cell death, optic nerve head excavation, and visual field loss. The discovery of a large, and growing, number of genetic and chromosomal loci has been shown to contribute to POAG risk, which carry implications for disease pathogenesis. Differential gene expression analyses in glaucoma-affected tissues as well as animal models of POAG are enhancing our mechanistic understanding in this common, blinding disorder. In this review we summarize recent developments in POAG genetics and molecular genetics research.

Epidemiological studies suggest that by 2020 the prevalence of primary open angle glaucoma (POAG) is estimated to increase to 76.0 million, and to 111.8 million by 2040 globally due to the population aging. The prevalence of POAG is the highest among those of African descent, followed by Asians, and the lowest in Europeans. POAG is a genetically complex trait with a substantial fraction exhibiting a significant heritability. Less than 10% of POAG cases in the general population are caused by specific gene mutations and the remaining cases are polygenic. Quantitative traits related to POAG pathogenesis such as intra-ocular pressure (IOP), vertical cup/disc ratio (VCDR), optic disc area, and central corneal thickness (CCT) are highly heritable, and likely to be influenced at least in part by genes and show substantial variation in human populations. Recent genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs) at different loci including CAV1/CAV2, TMCO1, CDKN2B-AS1, CDC7-TGFBR3, SIX1/SIX6, GAS7 and ATOH7 to be associated with POAG and its related quantitative traits (endophenotypes). The chapter provides a brief overview on the different GWAS and SNP association studies and their correlation with various clinical parameters important for POAG in the population worldwide, including the Middle East.