Glaucoma is the leading cause of irreversible blindness worldwide. Previous observational studies have suggested a relationship between central corneal thickness (CCT) and glaucoma; however, the results are inconsistent. This study aimed to investigate whether CCT is associated with a risk for developing open-angle glaucoma (OAG). We employed two-sample Mendelian randomization to assess the relationship between CCT and OAG, namely, primary open-angle glaucoma (POAG) and suspected glaucoma. Genetic instruments composed of variants associated with CCT at genome-wide significance (P < 5 × 10-8) were obtained from published genome-wide association studies from Iglesias et al. for discovery and Bonnemaijer et al. for replication. Summary-level statistics for these instruments for the OAG were obtained from the FinnGen Project (Release 10). Inverse-variance-weighted regression of genetic susceptibility predicted that increased CCT was positively associated with an increased risk for POAG (odds ratio [OR], 1.005; 95% confidence interval [CI], 1.002-1.008; P = 0.001) and suspected glaucoma (OR, 1.006; 95% CI, 1.003-1.009; P < 0.001). In the replication sample of CCT, increased CCT was also positively associated with an increased risk for POAG (OR, 1.004; 95% CI, 1.000-1.008; P = 0.029) and suspected glaucoma (OR, 1.005; 95% CI, 1.001-1.008; P = 0.013). We found genetic evidence supporting a potential causal association between increased CCT and the risk of POAG and suspected glaucoma in the European population. This findings indicates the clinical significance of CCT in the diagnosis and treatment of glaucoma. Further studies are needed to elucidate the underlying mechanisms of this causal relationship.

Interactions between trabecular meshwork (TM) cells and their extracellular matrix (ECM) are critical for normal outflow function in the healthy eye. Multifactorial dysregulation of the TM is the principal cause of elevated intraocular pressure that is strongly associated with glaucomatous vision loss. Key characteristics of the diseased TM are pathologic contraction and actin stress fiber assembly, contributing to overall tissue stiffening. Among first-line glaucoma medications, the Rho-associated kinase inhibitor (ROCKi) netarsudil is known to directly target the stiffened TM to improve outflow function via tissue relaxation involving focal adhesion and actin stress fiber disassembly. Yet, no in vitro studies have explored the effect of netarsudil on human TM (HTM) cell contractility and actin remodeling in a 3D ECM environment. Here, we use our bioengineered HTM cell-encapsulated ECM hydrogel to investigate the efficacy of different netarsudil-family ROCKi compounds on reversing pathologic contraction and actin stress fibers. Netarsudil and all related experimental ROCKi compounds exhibited significant ROCK1/2 inhibitory and focal adhesion disruption activities. Furthermore, all ROCKi compounds displayed potent contraction-reversing effects on HTM hydrogels upon glaucomatous induction in a dose-dependent manner, relatively consistent with their biochemical/cellular inhibitory activities. At their tailored EC50 levels, netarsudil-family ROCKi compounds exhibited distinct effect signatures of reversing pathologic HTM hydrogel contraction and actin stress fibers, independent of the cell strain used. Netarsudil outperformed the experimental ROCKi compounds in support of its clinical status. In contrast, at uniform EC50-levels using netarsudil as reference, all ROCKi compounds performed similarly. Collectively, our data suggest that netarsudil exhibits high potency to rescue HTM cell pathobiology in a tissue-mimetic 3D ECM microenvironment, solidifying the utility of our bioengineered hydrogel model as a viable screening platform to further our understanding of TM pathophysiology in glaucoma.

OBJECTIVE: To evaluate the effects of a water drinking test (WDT) on the intraocular pressure (IOP) and vascular density of the optic nerve head and macula in healthy individuals and those with primary open glaucoma using optical coherence tomography angiography.
METHODS: In this prospective comparative study, 30 healthy patients and 44 POAG subjects were divided into two groups. The study\'s outcome measures were the IOP and vessel density of the optic nerve and macular area. After ingesting 1000 ml of water in 5 min, the effect of the WDT on the IOP and the vascular density of the macular area and optic nerve head were measured at baseline and then 20, 40, and 60 min later at intervals of 20 min.
RESULTS: The initial IOP in the healthy and glaucomatous eye groups was comparable (15.94 ± 2.6 and 16.87 ± 4.21 mmHg, respectively, P = 0.506). The IOP of both groups peaked at 40\' measurements. POAG eyes had significantly higher IOP elevation (4.34 ± 0.30 vs. 2.24 ± 0.30 mmHg, P < 0.001). The glaucomatous eyes had lower radial peripapillary capillary (RPC) and whole macular superficial capillary plexus (SCP) densities at baseline (48.55 ± 5.99 vs. 51.33 ± 3.75) and (48.92 ± 3.41 vs. 45.29 ± 5.29), respectively (P < 0.001). After the WDT, the change in vessel density between groups in the RPC, whole superficial, and deep capillary plexuses was insignificant (SCP and DCP of 0.66 and 0.70, respectively, P = 0.16).
CONCLUSIONS: The WDT caused a significant IOP jump in both glaucomatous and healthy eyes, but generally, the alterations in the glaucomatous eyes were more pronounced. The changes in vascular density in the macula and optic nerve head were similar between the groups.

The trabecular meshwork (TM) from primary open-angle glaucoma (POAG) cases has been found to contain decreased levels of intracellular plasmalogens. Plasmalogens are a subset of lipids involved in diverse cellular processes such as intracellular signaling, membrane asymmetry, and protein regulation. Proper plasmalogen biosynthesis is regulated by rate-limiting enzyme fatty acyl-CoA reductase (Far1). ATPase phospholipid transporting 8B2 (ATP8B2) is a type IV P-type ATPase responsible for the asymmetric distribution of plasmalogens between the intracellular and extracellular leaflets of the plasma membranes. Here we describe the methodology for extraction and culturing of TM cells from corneal tissue and subsequent downregulation of ATP8B2 using siRNA transfection. Further quantification and downstream effects of ATP8B2 gene knockdown will be analyzed utilizing immunoblotting techniques.

The current primary approach to the therapeutic and surgical management of glaucoma is limited to lowering intraocular pressure (IOP). While normalization of IOP stabilizes some functional parameters, there is still potential for further restoration of lost visual function in the post-operative period while maintaining the \"therapeutic window\". Neuroprotection refers to the modification of retinal ganglion cells and the neuronal microenvironment to promote their survival and function. Numerous studies have identified effective neuroprotective methods for glaucoma; however, their implementation into clinical practice remains a significant challenge. This review presents the most clinically significant treatment strategies, as well as the latest therapeutic advances in physiotherapy.
Основной подход в терапевтическом и хирургическом лечении глаукомы на современном этапе ограничивается снижением внутриглазного давления, так как при нормализации данного параметра можно достигнуть стабилизации некоторых функциональных показателей. Тем не менее в отдаленном периоде после операции при сохранении «терапевтического окна» представляется возможным дополнительно развить часть утраченных зрительных функций. Нейропротекция — это модификация ганглиозных клеток сетчатки и микроокружения нейронов для содействия их выживанию и функционированию. Многочисленные исследования выявили эффективные методы нейропротекции глаукомы, тем не менее внедрение их в клиническую практику остается серьезной проблемой. В обзоре представлены наиболее клинически значимые стратегии лечения, а также последние терапевтические достижения в области физиотерапевтического лечения.

Background: To assess intraocular pressure (IOP) changes and complications after XEN45 implants in medically controlled eyes (MCE) vs. medically uncontrolled eyes (MUE). Methods: A retrospective study, in a tertiary referral hospital, on mild-to-moderate primary open-angle glaucoma (POAG) cases under topical medication, including 32 eyes with IOP < 21 mmHg (MCE group) and 30 eyes with IOP ≥ 21 mmHg (MUE group). The success criteria using Kaplan-Meier analysis was IOP < 21 mmHg without medications (complete success) or fewer drugs than preoperatively (qualified success) at the last visit, without new surgery or unresolved hypotony. Results: No significant preoperative differences were found between the groups. The mean IOP was 15.6 ± 3.8 mmHg in MCE and 15.1 ± 4.1 mmHg in the MUE group (p > 0.05; Mann-Whitney test) at the end of the follow-up (mean of 26.1 ± 15.6 months and 28.3 ± 15.3 months, respectively) (p = 0.414, Mann-Whitney Test). The device caused a significant IOP reduction at 24 h in both groups. Thereafter, the MCE group significantly tended to increase IOP, recovering baseline values at 1 month and maintaining them until the end of the follow-up. In contrast, in the MUE group, the IOP values tended to be similar after the first reduction. No relevant complications and no significant differences between the groups in the survival analysis were found. Conclusions: XEN45 provided stable IOP control in both the MCE and MUE group without important complications in the medium term. The IOP increasing in the MCE group, after a prior decrease, led to restored baseline values 1 month after surgery. The homeostatic mechanism that causes the rise in the IOP to baseline values and its relationship with failure cases remains to be clarified.

Primary open-angle glaucoma (POAG) is a progressive optic neuropathy with a complex, multifactorial aetiology. Raised intraocular pressure (IOP) is the most important clinically modifiable risk factor for POAG. All current pharmacological agents target aqueous humour dynamics to lower IOP. Newer therapeutic agents are required as some patients with POAG show a limited therapeutic response or develop ocular and systemic side effects to topical medication. Elevated IOP in POAG results from cellular and molecular changes in the trabecular meshwork driven by increased levels of transforming growth factor β (TGFβ) in the anterior segment of the eye. Understanding how TGFβ affects both the structural and functional changes in the outflow pathway and IOP is required to develop new glaucoma therapies that target the molecular pathology in the trabecular meshwork. In this study, we evaluated the effects of TGF-β1 and -β2 treatment on miRNA expression in cultured human primary trabecular meshwork cells. Our findings are presented in terms of specific miRNAs (miRNA-centric), but given miRNAs work in networks to control cellular pathways and processes, a pathway-centric view of miRNA action is also reported. Evaluating TGFβ-responsive miRNA expression in trabecular meshwork cells will further our understanding of the important pathways and changes involved in the pathogenesis of glaucoma and could lead to the development of miRNAs as new therapeutic modalities in glaucoma.

OBJECTIVE: To investigate that the changes of lamina cribrosa (LC) thickness and depth after latanoprost therapy in primary open-angle glaucoma (POAG) and ocular hypertension (OHT) patients.
METHODS: In this single-center prospective cross-sectional study, 35 eyes from 35 patients with POAG or OHT (study group) and 26 age- and gender- matched healthy individuals (control group) were included. All participants were examined by spectral domain optical coherence tomography (SD-OCT) with enhanced depth imaging (EDI) mode for LC thickness and depth measurements at the first visit before latanoprost therapy and at visits after 1 (second visit) and 3 (third visit) months of latanoprost therapy.
RESULTS: The mean LC thickness in both horizontal and vertical scans of the study group were thinner than the control group (p < 0.001, for both). During latanoprost therapy in the study group, the LC thickness values in horizontal scans significantly differed over the three visits, gradually increased (p < 0.05). There was significantly decrease in LC depth in horizontal scans between the first and third visits, and the second and third visits (p = 0.003 and p = 0.008, respectively). The gradual decrease in LC depth in vertical scans was observed at all visits, but the statistically significant difference was between the first and third visits only (p = 0.048).
CONCLUSIONS: POAG/OHT patients showed more LC thinning compared with healthy individuals. The significant increase in LC thickness and the significant decrease in LC depth were detected after IOP reduction therapy with latanoprost in ocular hypertensive/ glaucomatous eyes.

OBJECTIVE: To describe the outcomes of double implantation of Xen 45 Gel Stent (Xen) using an ab externo approach with closed conjunctiva.
METHODS: Retrospective single-centre case series of primary open-angle glaucoma patients with at least six months of follow-up after implantation of a second Xen in the same eye via ab externo technique without conjunctival opening.
RESULTS: Eight pseudophakic eyes of 8 patients were included. Intraocular pressure (IOP) dropped from 30 ± 2.6 mmHg pre-operatively to 22.4 ± 2.3 mmHg one month after the first Xen implant (mean difference: -7.6 mmHg [95% confidence interval: -9.4, -5.9 mmHg], p = 0.0092). A second Xen was then implanted to achieve the target IOP. The procedure showed no significant intraoperative or postoperative complications. The IOP dropped to 16.1 ± 2.7 mmHg six months following this second implant (mean difference: -6.3 mmHg [95% confidence interval: -7.2, -5.3 mmHg], p = 0.0183); however, 3 patients needed medical therapy to further reduce the IOP towards the target value.
CONCLUSIONS: Sequential implantation of two Xen 45 Gel Stents using an ab externo approach with closed conjunctiva appears a promising procedure that showed a favorable safety and efficacy profile in this small case series. This pilot data might pave the way for further studies to evaluate the safety and efficacy of the procedure.

[This corrects the article DOI: 10.3389/fcvm.2022.1024044.].