Glanatec (ripasudil) / Kowa - LARVOL DELTA

Exploring the potential of Rho kinase inhibitors in ophthalmology: From mechanisms to clinical practice. (PubMed, Surv Ophthalmol) - "We performed a systematic database search in Ovid MEDLINE and Ovid Embase on 5th April 2022 using the following keywords: 'primary open angle glaucoma', 'glaucoma surgery', 'corneal wound healing', 'corneal endothelial dysfunction', 'diabetic retinopathy', 'diabetic macular oedema', 'age-related macular degeneration', 'rho kinase inhibitor', 'rho-kinase inhibitor', rock inhibitor', 'ripasudil', 'netarsudil' and 'fasudil'. Additionally, ROCK inhibitors show promise in enhancing endothelial cell migration, thus providing a novel treatment avenue for corneal diseases such as Fuchs endothelial dystrophy. In retinal conditions, including diabetic retinopathy and age-related macular degeneration, ROCK inhibitors reduce vascular permeability, inflammation, and fibrosis, stabilising disease progression."

Journal • Review • Age-related Macular Degeneration • Diabetic Macular Edema • Diabetic Retinopathy • Fibrosis • Glaucoma • Immunology • Inflammation • Macular Degeneration • Macular Edema • Ophthalmology • Retinal Disorders

Ponatinib and other clinically approved inhibitors of Src and Rho-A kinases abrogate dengue virus serotype 2- induced endothelial permeability. (PubMed, Virulence) - "Here, we show that the FDA-approved SFK inhibitors Bosutinib, Vandetanib and Ponatinib, as well as the ROCK inhibitors, Netarsudil and Ripasudil significantly inhibit DENV2-induced endothelial permeability. Comparable effects were observed even when ponatinib treatment was initiated after symptom onset. The results highlight ponatinib as an effective therapeutic option in severe dengue; and also a similar potential for other FDA- approved SFK and ROCK inhibitors."

Journal • Dengue Fever • Hematological Disorders • Infectious Disease • Thrombocytopenia • CDH5 • IL1B • RHOA • TNFA

Rho Kinase Inhibitors in Glaucoma Management: Current Perspectives and Future Directions. (PubMed, Drug Des Devel Ther) - "Recent clinical studies assessing the efficacy and safety of Ripasudil (K-115) and Netarsudil (AR-13324) have demonstrated promising outcomes in the treatment of various types of glaucoma. This review aims to provide an overview of ROCK inhibitors, focusing on their mechanisms of action, clinical efficacy, safety profiles, and additional benefits for eye health. Furthermore, further potential applications of ROCK inhibitors in glaucoma management are going to be discussed."

Journal • Review • Conjunctivitis • Dry Eye Disease • Glaucoma • Ocular Infections • Ocular Inflammation • Ophthalmology

AI Algorithm Aids Morphological Validation in Cell Therapy Products (ARVO 2025) - "Conclusions The AI-based algorithm demonstrated robust detection of fibroblastic changes in Ripasudil-treated EO2002 cells. Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details."

Ophthalmology

Inhibitory effect of ripasudil on proliferative vitreoretinopathy (ARVO 2025) - "Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details."

Ophthalmology • Retinal Disorders • GJA1 • S100A4 • TERC

Effect of Co-Delivery of Ripasudil and Dexamethasone on Gene Expressions in Human Trabecular Meshwork Cells for Potential Prevention of Glucocorticoid-Induced Ocular Hypertension (ARVO 2025) - "However, some contradictory results in gene expression, particularly for genes like sFRP1 and WIN7B, suggest that the response to the drugs may vary depending on whether the cells are susceptible to Dex. This highlights the complexity of drug interactions and gene regulation in glaucoma treatment."

Glaucoma • Ophthalmology • ACTA2 • COL11A1 • COL1A1 • ECM2 • ROR1 • SFRP1

Descemet Stripping Only combined with Ripasudil for treating Fuchs dystrophy at a leading Center in Spain. (ARVO 2025) - "Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details."

Cataract • Ophthalmology

Rho kinase inhibitor liposomal therapy for preventing Fuchs endothelial corneal dystrophy progression (ARVO 2025) - "We aimed to develop eye drops containing rho kinase inhibitors (RKIs) encapsulated in liposomes conjugated with transferrin (TF receptor; upregulated biomarker in FECD) for targeting enhanced uptake by corneal endothelial cells (CECs) in FECD and compare the toxicity and efficacy of two different RKI formulations (ripasudil vs. netarsudil liposomes) to prevent FECD progression. Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details."

Ophthalmology • COL8A2

Ripasudil does not induce phospholipid accumulation in human corneal epithelial cells. (PubMed, Exp Eye Res) - "Netarsudil, a ROCK inhibitor, is known to induce cornea verticillata as an adverse effect in clinical settings. Unlike systemic amiodarone and antimalarials, topical agents do not typically induce the development of this corneal condition...In contrast, ripasudil and Y-27632 lack these structural features. Our results suggest that ripasudil has a low likelihood of inducing cornea verticillata."

Journal • Glaucoma • Infectious Disease • Ophthalmology

Clinical implications of lowering episcleral venous pressure in the management of glaucoma and the use of Rho kinase inhibitors. (PubMed, Surv Ophthalmol) - "Regardless of the relatively modest EVP reductions achieved with current treatments, EVP lowering may have clinical significance in patients with glaucoma, particularly those with low intraocular pressure (IOP). Those who might benefit include patients with elevated EVP; normal-tension glaucoma; undergoing trabecular meshwork bypass surgery, goniotomy, or selective laser trabeculoplasty; or requiring additional IOP lowering to the low teens or with a lower-than-usual target IOP."

Journal • Review • Glaucoma • Ophthalmology

A Study to Investigate the Safety and Efficacy of K-321 Eye Drops After Simultaneous Cataract Surgery and Descemetorhexis in Participants With Fuchs Endothelial Corneal Dystrophy (FECD) (clinicaltrials.gov) - P3 | N=110 | Active, not recruiting | Sponsor: Kowa Research Institute, Inc. | Trial primary completion date: Oct 2024 ➔ Jan 2025

Trial primary completion date • Cataract • Ophthalmology • Transplantation

A Study to Evaluate the Safety and Efficacy of K-321 Eye Drops After Descemetorhexis in Participants With Fuchs Endothelial Corneal Dystrophy (FECD) (clinicaltrials.gov) - P3 | N=107 | Active, not recruiting | Sponsor: Kowa Research Institute, Inc. | Trial completion date: Dec 2025 ➔ Mar 2026 | Trial primary completion date: Dec 2024 ➔ Jun 2025 | Recruiting ➔ Active, not recruiting

Enrollment closed • Trial completion date • Trial primary completion date • Ophthalmology • Transplantation

Anti-inflammatory actions of ripasudil ameliorate experimental autoimmune uveoretinitis in the acute phase. (PubMed, BMJ Open Ophthalmol) - "Ripasudil suppressed EAU when administered from the onset of the disease by inhibiting cells that strongly express genes involved in the ROCK signalling pathway and differentiate into Th1 cells."

Journal • Genetic Disorders • Immunology • Inflammation • Ocular Inflammation • Ophthalmology • Retinal Disorders • Uveitis

PPARα regulates YAP protein levels and activity by affecting its ubiquitination modification. (PubMed, BMC Biol) - "These findings highlight the pivotal role of ubiquitination in regulating YAP through PPARα activation, providing novel insights for future studies on the post-translational regulation of YAP by PPARα activation."

Journal • Hepatology • Targeted Protein Degradation • PPARA • TRAF6

Drug- and Cell-Type-Specific Effects of ROCK Inhibitors as a Potential Cause of Reticular Corneal Epithelial Edema. (PubMed, Cells) - "To explain the potential mechanisms, we comparatively analyzed the effects of ripasudil and netarsudil on corneal endothelial and epithelial function in vitro...Reticular bullous corneal epithelial edema was observed in a patient following netarsudil 0.02%/latanoprost 0.005% ophthalmic solution (Roclanda®) for elevated intraocular pressure...The expression changes normalized after discontinuation of ROCK inhibitors. The findings support the concept that ROCK inhibitors can act as a double-edged sword by having beneficial effects on corneal endothelial cells and adverse effects on epithelial cells."

Journal • Glaucoma • Ophthalmology

Short-term safety and efficacy of ripasudil as "add-on therapy" in glaucoma patients on maximum tolerable glaucoma medication. (PubMed, Saudi J Ophthalmol) - "Ripasudil is effective and tolerable in POAG patients already on maximal medical therapy. It can be utilized as an extra tool that can postpone invasive procedures, especially in the short term."

Journal • Dry Eye Disease • Glaucoma • Ocular Inflammation • Ophthalmology

Efficacy of the Rho-Kinase Inhibitor for Corneal Endothelial Protection in Fuchs Endothelial Corneal Dystrophy After Phacoemulsification. (PubMed, Cornea) - "The topical ROCK inhibitor, or ripasudil, demonstrated beneficial effects on preventing endothelial cell loss and improving endothelial function in patients with FECD undergoing phacoemulsification. Corneal densitometry showed reduced corneal light scattering in the ripasudil group after phacoemulsification, suggesting improved corneal endothelial function."

Journal • Cataract • Dermatology • Ophthalmology • Transplantation

The Effects of Ripasudil in Patients with FED Undergoing Femtosecond Laser Assisted Cataract Surgery (clinicaltrials.gov) - P3 | N=120 | Recruiting | Sponsor: Singapore Eye Research Institute | Trial primary completion date: Jul 2024 ➔ Jul 2025

Trial primary completion date • Cataract • Ophthalmology

Effect of Ripasudil on the Change Rates of the Circumpapillary Retinal Nerve Fiber Layer Thickness in Patients With Primary Open-Angle Glaucoma. (PubMed, J Ophthalmol) - "After adjusting for IOP changes, the improvement in cpRNFLT change rate was 0.33 ± 0.23 μm/year, albeit not statistically significant. The cpRNFLT change rate significantly increased after ripasudil administration, whereas the contribution of the IOP decline was not significant."

Journal • Glaucoma • Ophthalmology

DETECT II: Descemet Endothelial Thickness Comparison Trial II (clinicaltrials.gov) - P3 | N=60 | Recruiting | Sponsor: Stanford University | Trial completion date: Nov 2027 ➔ Aug 2028 | Trial primary completion date: Nov 2026 ➔ Aug 2027

Trial completion date • Trial primary completion date • Ophthalmology

DETECT I: Descemet Endothelial Thickness Comparison Trial I (clinicaltrials.gov) - P3 | N=160 | Recruiting | Sponsor: Stanford University | Trial completion date: Mar 2027 ➔ Aug 2027 | Trial primary completion date: Mar 2026 ➔ Jul 2026

Trial completion date • Trial primary completion date

Late-Onset Ocular Hypotensive Effect of Ripasudil on Primary Open-Angle Glaucoma. (PubMed, Clin Ophthalmol) - "Some patients with POAG showed the late-onset IOP-lowering effect of ripasudil, and its associated factors were higher IOP and thicker RNFL. The addition of ripasudil may offer potential benefits particularly for early-stage glaucoma with thicker RNFL."

Journal • Cardiovascular • Glaucoma • Ophthalmology

Ripasudil's paradox: bullous keratopathy with honeycomb twist. (PubMed, BMJ Case Rep) - "This case highlights the complexity of ripasudil's effects on corneal endothelium, showing a paradoxical response. Timely identification of ripasudil-induced keratopathy is crucial, particularly in cases when it is started elsewhere, emphasising the necessity for vigilant monitoring and management strategies."

Journal • Glaucoma • Ophthalmology

Importance of benzoyltransferase GcnE and lysine benzoylation of alcohol dehydrogenase AdhB in pathogenesis and aflatoxin production in Aspergillus flavus. (PubMed, mBio) - "Our data demonstrated that alcohol dehydrogenase B (AdhB) is regulated by benzoylation on lysine 321 (K321), and mutations of Kbz site in AdhB significantly reduced the alcohol dehydrogenase activity in vivo and in vitro...Here, we first identified 46 benzoylated proteins in A. flavus, and found that benzoyltransferase GcnE exerted effects on pathogenicity and aflatoxin production by regulating the benzoylation of AdhB. This finding not only provided valuable information for prevention and control of A. flavus contamination, but also offered basic knowledge for investigation of the regulation mechanism of secondary metabolism in other fungi."

Journal

The Mechanisms of Neuroprotection by Topical Rho Kinase Inhibition in Experimental Mouse Glaucoma and Optic Neuropathy. (PubMed, Invest Ophthalmol Vis Sci) - "The purpose of this study was to delineate the neuroprotective mechanisms of topical 2% ripasudil (Rip), a Rho kinase (ROCK) inhibitor...Topical Rip reduced RGC loss in GL and ON crush, with suppression of ROCK signaling in the retina and ON. The neuroprotection mechanisms appear to involve effects on both RGC and astrocyte responses to IOP elevation."

Journal • Preclinical • Glaucoma • Ocular Inflammation • Ophthalmology • Optic Neuritis • Pain • APP • RBPMS