Crossover Randomized Study of Pharmacologic Effects of Ripasudil-Brimonidine Fixed-Dose Combination Versus Ripasudil or Brimonidine.

Introduction: Multidrug regimens for glaucoma treatment often result in adherence issues due to inconvenience; these issues may be improved with fixed-dose combination drugs. The ophthalmic solution of ripasudil-brimonidine fixed-dose combination (RBFC; K-232) is the first treatment combining a Rho kinase inhibitor and an α-adrenoceptor agonist, and has demonstrated ability to lower intraocular pressure (IOP) and have various effects on conjunctival hyperemia and corneal endothelial cell morphology. This study evaluates the pharmacologic effects of RBFC treatment versus its separate components-ripasudil or brimonidine.

Ripasudil-Brimonidine Fixed-Dose Combination vs Ripasudil or Brimonidine: Two Phase 3 Randomized Clinical Trials.

Purpose: To confirm the superiority of the intraocular pressure (IOP)-lowering effect of the ripasudil-brimonidine fixed-dose combination (RBFC, K-232) to ripasudil 0.4% or brimonidine 0.1% ophthalmic solution.

Elevated soluble vascular endothelial growth factor receptor levels in aqueous humor from patients with different types of glaucoma.

We investigated the aqueous humor levels of vascular endothelial growth factor (VEGF), soluble VEGF receptor (sVEGFR)1, and sVEGFR2 in glaucoma patients and the correlations among them. Aqueous humor was collected from the anterior chamber at the start of glaucoma or cataract surgery. The levels of VEGF and its receptors, sVEGFR1 and sVEGFR2, were measured using multiplex bead-based immunoassays.

Long-Term Intraocular Pressure-Lowering Effects and Adverse Events of Ripasudil in Patients with Glaucoma or Ocular Hypertension over 24 Months.

Introduction: Glaucoma is a leading cause of irreversible blindness and ripasudil was the first Rho kinase inhibitor approved as antiglaucoma medication. Here we present the final analysis of the ROCK-J study, a large-scale post-marketing surveillance study to evaluate the long-term safety and effectiveness of ripasudil in Japanese patients with glaucoma or ocular hypertension in a real-word clinical setting.

Methods: ROCK-J was a 24-month, prospective, open-label, observational study that included ripasudil-naïve patients with glaucoma or ocular hypertension who were initiating treatment with ripasudil according to the Japanese approved indication between June 1, 2015 and April 30, 2017.

Suberoylanilide hydroxamic acid (SAHA) inhibits transforming growth factor-beta 2-induced increases in aqueous humor outflow resistance.

Transforming growth factor-beta 2 (TGF-β2) is highly concentrated in the aqueous humor of primary open-angle glaucoma patients. TGF-β2 causes fibrosis of outflow tissues, such as the trabecular meshwork (TM), and increases intraocular pressure by increasing resistance to aqueous humor outflow. Recently, histone deacetylase (HDAC) activity was investigated in fibrosis in various tissues, revealing that HDAC inhibitors suppress tissue fibrosis.

Intraocular Pressure-Lowering Effects of Trabeculectomy Versus MicroShunt Insertion in Rabbit Eyes.

Purpose: To compare the surgical results of PRESERFLO MicroShunt (MicroShunt) insertion and trabeculectomy in rabbit eyes.

Methods: Trabeculectomy or MicroShunt insertion was performed on the eyes of Japanese white rabbits. Intraocular pressure (IOP) was measured on conscious rabbits using a rebound tonometer for up to 12 weeks after surgery.

Potential roles of the IL-6 family in conjunctival fibrosis.

Elevated intraocular pressure (IOP) is a significant risk factor for vision loss due to glaucoma, which is a major cause of blindness worldwide. Glaucoma filtration surgery (GFS) is an important method to reduce IOP by guidance of aqueous humor into a newly built filtration bleb in the conjunctiva; management of the wound healing mechanism is essential for the success of GFS. Here, we investigated the roles of interleukin (IL)-6 family members during the wound healing process after GFS.

Correction: TGF-β-induced activation of conjunctival fibroblasts is modulated by FGF-2 and substratum stiffness.

[This corrects the article DOI: 10.1371/journal.pone.

N-methyladenosine (mA) is an endogenous A3 adenosine receptor ligand.

About 150 post-transcriptional RNA modifications have been identified in all kingdoms of life. During RNA catabolism, most modified nucleosides are resistant to degradation and are released into the extracellular space. In this study, we explored the physiological role of these extracellular modified nucleosides and found that N-methyladenosine (mA), widely recognized as an epigenetic mark in RNA, acts as a ligand for the human adenosine A3 receptor, for which it has greater affinity than unmodified adenosine.

TGF-β-induced activation of conjunctival fibroblasts is modulated by FGF-2 and substratum stiffness.

Purpose: This study aimed to investigate the effects of substratum stiffness on the sensitivity of human conjunctival fibroblasts to transforming growth factor (TGF)-β, and to explore the molecular mechanism of action.

Methods: Human conjunctival fibroblasts were cultured on collagen-coated plastic or silicone plates. The stiffness of the silicone plates was 0.

Correction to: Safety and efficacy of ripasudil in Japanese patients with glaucoma or ocular hypertension: 12-month interim analysis of ROCK-J, a post-marketing surveillance study.

An amendment to this paper has been published and can be accessed via the original article.

RhoA Activation Decreases Phagocytosis of Trabecular Meshwork Cells.

Purpose: RhoA signaling is important for the regulation of intraocular pressure through the trabecular meshwork (TM). However, the relationship between RhoA signaling and phagocytosis in TM cells is unclear. The purpose of this study was to investigate the effects of RhoA signaling on the phagocytosis of TM cells.

Spatial and Temporal Relationship between Structural Progression and Disc Hemorrhage in Glaucoma in a 3-Year Prospective Study.

Purpose: To investigate the spatial and temporal relationship between disc hemorrhage (DH) and structural progression in patients with primary open-angle glaucoma (POAG) in a 3-year prospective study.

Design: Prospective cohort study.

Participants: Patients with POAG and intraocular pressure of ≤18 mmHg on monotherapy with prostaglandin analogs.

Safety and efficacy of ripasudil in Japanese patients with glaucoma or ocular hypertension: 12-month interim analysis of ROCK-J, a post-marketing surveillance study.

Background: Ripasudil is approved in Japan for glaucoma or ocular hypertension (OH) when other treatments are ineffective or cannot be administered. Its long-term safety and efficacy are being examined in a post-marketing surveillance study; 12-month data are described here.

Methods: This prospective, open-label, observational study enrolled patients with glaucoma or OH who started ripasudil during routine care.

Clinical Features of Disaster-Associated Direct Deaths during Recent Inland Earthquakes in Japan.

Natural disasters, including earthquakes, cause disaster-associated direct deaths due to hazards and disaster-related deaths. This study was a retrospective and observational study that explored the effect of natural disasters on direct death. Although research reports on disaster-related deaths are common, there are few reports of disaster-associated direct death caused by events, such as house collapses, fires, and sediment-related factors.

Intraocular pressure-lowering effects of ripasudil in uveitic glaucoma, exfoliation glaucoma, and steroid-induced glaucoma patients: ROCK-S, a multicentre historical cohort study.

To evaluate the efficacy and safety of ripasudil for treatment of secondary glaucoma, a historical cohort study was conducted at 18 centres in Japan. Adults (age ≥20 years) who needed additional IOP reduction and received topical 0.4% ripasudil between 2014 and 2018 due to three secondary glaucoma subtypes, including uveitic glaucoma (UG), exfoliation glaucoma (EG) or steroid-induced glaucoma (SG) were assessed for mean IOP change from baseline prior to additional treatment with ripasudil.

The angiogenic effects of exosomes secreted from retinal pigment epithelial cells on endothelial cells.

Exosomes are informative microvesicles associated with intercellular communication via the transfer of many molecular constituents such as proteins, lipids, and nucleic acids; environmental changes and the cellular status around cells greatly affect exosome components. Cells of the retinal pigment epithelium (RPE) are key players in retinal homeostasis. Transforming growth factor (TGF)-β and tumour necrosis factor (TNF)-α are increased in the vitreous and retina in several retinal diseases and activate and undergo epithelial-mesenchymal transition (EMT) in RPE cells.

Changes in corneal endothelial cell shape after treatment with one drop of ROCK inhibitor.

Purpose: We performed an investigation of the temporal impact on corneal endothelial cell (CEC) shape after ophthalmic instillation of one drop of the ROCK inhibitor, ripasudil.

Methods: Subjects comprised 32 healthy adult volunteers, each of whom instilled ripasudil in the right eye. CEC shape [defined as CEC density (CECD), coefficient of variation (CV), and hexagonal cell rate (6A)], central corneal thickness (CCT), intraocular pressure (IOP), and conjunctival hyperemia were evaluated before instillation (baseline) and at 15 min, 1 h, 2 h, and 4-6 h after instillation by non-contact specular microscopy and slit-lamp microscopy.

DNA methyltransferase inhibitor suppresses fibrogenetic changes in human conjunctival fibroblasts.

Purpose: This study aimed to clarify the effects of a DNA methyltransferase inhibitor on fibrogenetic changes in human conjunctival fibroblasts (HConF).

Methods: HConF were pretreated with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-Aza-dC) for 48 h. After one passage, the cells were treated with 5 ng/ml of transforming growth factor (TGF)-β2 for 48 h, and the expression levels of α-smooth muscle actin (α-SMA), extracellular matrix proteins, and phosphorylated Smad3 were evaluated with western blotting.

Early bleb parameters as long-term prognostic factors for surgical success: a retrospective observational study using three-dimensional anterior-segment optical coherence tomography.

Background: The object of this study is to investigate the effect of early bleb parameters measured by three-dimensional anterior-segment optical coherence tomography on the surgical success of trabeculectomy.

Methods: This retrospective study included 45 patients with 19 of exfoliation glaucoma, 17 of primary open angle glaucoma, 4 of neovascular glaucoma, 4 of uveitic glaucoma and 1 of glaucoma caused from familial amyloid polyneuropathy who underwent trabeculectomy. Bleb parameters, such as total bleb height, the position and the width of filtration openings on the scleral flap, bleb wall thickness, fluid-filled cavity height, and bleb wall intensity were assessed by three-dimensional anterior-segment optical coherence tomography 0.

Correction to: Safety and Efficacy of Ripasudil in Japanese Patients with Glaucoma or Ocular Hypertension: 3-month Interim Analysis of ROCK-J, a Post-Marketing Surveillance Study.

In the original publication values in the results section are incorrect. Errors were also identified in Fig. 5.

Efficacy and safety of Ex-PRESS® mini shunt surgery versus trabeculectomy for neovascular glaucoma: a retrospective comparative study.

Background: The objective of this study is to evaluate and compare the short-term efficacy and safety of Ex-PRESS® mini shunt surgery and trabeculectomy for neovascular glaucoma (NVG).

Methods: Patients with NVG who underwent Ex-PRESS® mini shunt surgery or trabeculectomy as a primary glaucoma surgery between March 2013 and October 2015 were included in the study, and their medical charts were retrospectively reviewed. The Ex-PRESS® and trabeculectomy groups included 14 eyes and 30 eyes, respectively.