glanatec and Glaucoma--Open-Angle

Currently, corneal blindness is affecting >10 million individuals worldwide, and there is a significant unmet medical need because only 1.5% of transplantation needs are met globally due to a lack of high-quality grafts. In light of this global health disaster, researchers are developing corneal substitutes that can resemble the human cornea

Topics: Corneal Injuries; Corneal Transplantation; Endothelium, Corneal; Glaucoma, Open-Angle; Humans; rho-Associated Kinases

In an elegant example of bench-to-bedside research, a hypothesis that cells in the outflow pathway actively regulate conventional outflow resistance was proposed in the 1990s and systematically pursued, exposing novel cellular and molecular mechanisms of intraocular pressure (IOP) regulation. The critical discovery that pharmacologic manipulation of the cytoskeleton of outflow pathway cells decreased outflow resistance placed a spotlight on the Rho kinase pathway that was known to regulate the cytoskeleton. Ultimately, a search for Rho kinase inhibitors led to the discovery of several molecules of therapeutic interest, leaving us today with 2 new ocular hypotensive agents approved for clinical use: ripasudil in Japan and netarsudil in the United States. These represent members of the first new class of clinically useful ocular hypotensive agents since the US Food and Drug Administration approval of latanoprost in 1996. The development of Rho kinase inhibitors as a class of medications to lower IOP in patients with glaucoma and ocular hypertension represents a triumph in translational research. Rho kinase inhibitors are effective alone or when combined with other known ocular hypotensive medications. They also offer the possibility of neuroprotective activity, a favorable impact on ocular blood flow, and even an antifibrotic effect that may prove useful in conventional glaucoma surgery. Local adverse effects, however, including conjunctival hyperemia, subconjunctival hemorrhages, and cornea verticillata, are common. Development of Rho kinase inhibitors targeted to the cells of the outflow pathway and the retina may allow these agents to have even greater clinical impact. The objectives of this review are to describe the basic science underlying the development of Rho kinase inhibitors as a therapy to lower IOP and to summarize the results of the clinical studies reported to date. The neuroprotective and vasoactive properties of Rho kinase inhibitors, as well as the antifibrotic properties, of these agents are reviewed in the context of their possible role in the medical and surgical treatment of glaucoma.

Topics: Antihypertensive Agents; Aqueous Humor; Benzoates; beta-Alanine; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Isoquinolines; Ocular Hypertension; rho-Associated Kinases; Sulfonamides; Translational Research, Biomedical

Primary open-angle glaucoma (OAG) affects approximately 45 million people worldwide and more than 2.5 million people aged 40 years or older in the United States. Pharmacologic treatment for glaucoma is directed towards lowering intraocular pressure (IOP) to slow disease progression and delay visual field loss. Current medical treatment options for the lowering of IOP include the following classes of topical medications: beta-adrenergic antagonists, alpha-adrenergic agonists, cholinergic agonists, carbonic anhydrase inhibitors, and prostaglandin analogs. Issues with existing drugs include failure to achieve target IOP with monotherapy, drug-related side effects, and low patient compliance with multiple daily administration of eye drops. In recent years, the scientific and medical community has seen encouraging development of novel classes of drugs for primary OAG, the majority of which lower IOP by targeting the trabecular meshwork outflow pathway to increase aqueous humor outflow. Among the most promising new pharmacologic candidates are rho kinase inhibitors including ripasudil (K-115), netarsudil (AR-13324), and AMA0076; adenosine receptor agonists including trabodenoson (INO-8875); and modified prostaglandin analogs including latanoprostene bunod (LBN, BOL-303259-X) and ONO-9054. This study aims to systematically review and summarize the most recent developments in clinical trials for new pharmacologic options for the treatment of primary open-angle glaucoma.

Topics: Glaucoma, Open-Angle; Humans; Intraocular Pressure; Isoquinolines; Oxepins; Prostaglandins F, Synthetic; rho-Associated Kinases; Sulfonamides

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.. Two prospective multicenter, randomized, double- or single-masked, active-controlled, phase 3 trials.. Patients with primary open-angle glaucoma or ocular hypertension whose IOP level was ≥18 mm Hg during treatment with ripasudil or brimonidine alone were randomized to 2 groups (RBFC and ripasudil) in a 1:1 ratio in the ripasudil-controlled trial and to 3 groups (RBFC, brimonidine, and ripasudil-brimonidine combination) in a 2:2:1 ratio in the brimonidine-controlled trial. The allocated study drugs were instilled twice daily for 8 weeks. The primary efficacy endpoint was the change in IOP 2 hours after instillation (11 AM) from the baseline to weeks 4, 6, and 8.. There were 206 patients randomized in the ripasudil-controlled trial. Changes in IOP were -2.6 and -1.2 mm Hg in the RBFC and ripasudil groups, respectively, with a difference of -1.4 mm Hg (95% CI = -1.8 to -1.0 mm Hg; P < .001). There were 282 randomized patients in the brimonidine-controlled trial. Changes in IOP were -3.4 and -1.5 mm Hg in the RBFC and brimonidine groups, respectively, with a difference of -1.8 mm Hg (95% CI = -2.3 to -1.4 mm Hg; P < .001). The most frequent adverse event was conjunctival hyperemia.. The IOP-lowering effect of RBFC was superior to that of ripasudil or brimonidine.

Topics: Antihypertensive Agents; Brimonidine Tartrate; Double-Blind Method; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Ocular Hypertension; Prospective Studies; Quinoxalines; Randomized Controlled Trials as Topic; Treatment Outcome

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. This single-center, prospective, randomized, open-label, blinded endpoint study with 3 × 3 crossover design randomly assigned healthy adult men to three groups (1:1:1) to undergo consecutive 8-day administration phases (with drug-free intervals of at least 5 days). Subjects received twice-daily instillation of RBFC → ripasudil → brimonidine (group A), ripasudil → brimonidine → RBFC (group B), or brimonidine → RBFC → ripasudil (group C). Endpoints included change in IOP, severity of conjunctival hyperemia, corneal endothelial cell morphology, pupil diameter, and pharmacokinetics.. Eighteen subjects were assigned in total (six to each group). RBFC significantly reduced IOP from baseline at 1 h post-instillation on days 1 and 8 (12.7 vs. 9.1 and 9.0 mmHg, respectively; both P < 0.001), and provided significantly greater IOP reductions than ripasudil or brimonidine at several time points. The most common adverse drug reaction with all three treatments was mild conjunctival hyperemia, which transiently increased in severity with RBFC or ripasudil, peaking at 15 min post-instillation. In post hoc analyses, conjunctival hyperemia scores were lower with RBFC than with ripasudil at several time points. Transient morphologic changes in corneal endothelial cells occurred for up to several hours with RBFC or ripasudil, but not with brimonidine. Pupil diameter did not change with RBFC.. RBFC significantly reduced IOP compared with each agent alone. A combination of each agent's pharmacologic profile was observed in that of RBFC.. Japan Registry of Clinical Trials; Registration No. jRCT2080225220.

Topics: Adult; Antihypertensive Agents; Brimonidine Tartrate; Endothelial Cells; Glaucoma, Open-Angle; Humans; Hyperemia; Intraocular Pressure; Male; Ocular Hypertension; Ophthalmic Solutions; Prospective Studies; Quinoxalines

A clinical trial evaluated ocular hypotensive efficacy and safety of netarsudil 0.02% once daily (QD) relative to ripasudil 0.4% twice daily (BID).. This was a single-masked, randomized, phase 3, superiority study. Japanese patients were randomized to either the netarsudil 0.02% group or the ripasudil 0.4% group in a 1:1 ratio and treated for 4 weeks. The primary efficacy variable was mean diurnal intraocular pressure (IOP) (average of diurnal time points at 09:00, 11:00, and 16:00) at Week 4.. A total of 245 patients were included in the primary analysis. At Week 4, least squares (LS) mean of diurnal IOP adjusted for baseline was 15.96 and 17.71 mmHg in the netarsudil 0.02% and ripasudil 0.4% groups, respectively, demonstrating the superiority of netarsudil 0.02% QD over ripasudil 0.4% BID by a margin of - 1.74 mmHg (p < 0.0001). Mean reduction from baseline in mean diurnal IOP at Week 4 was 4.65 and 2.98 mmHg, respectively. Adverse events (AEs) occurred less frequently in netarsudil 0.02% than in ripasudil 0.4%, with the incidence of ocular AEs being 59.8% and 66.7%, respectively. The most frequently reported AE was conjunctival hyperemia in both groups, with an incidence of 54.9% and 62.6%, respectively. No serious eye-related AEs were reported.. Netarsudil ophthalmic solution 0.02% dosed QD (p.m.) was well tolerated and more effective in reducing IOP than ripasudil ophthalmic solution 0.4% dosed BID. Netarsudil 0.02% QD may become an important option for the treatment of Japanese patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT).. ClinicalTrials.gov identifier, NCT04620135.

Topics: Glaucoma, Open-Angle; Humans; Intraocular Pressure; Japan; Ocular Hypertension; rho-Associated Kinases

Glaucoma leads to irreversible blindness. Numerous anti-glaucoma eye drops have been developed. Unfortunately, many patients with glaucoma still suffer from progressive visual disorders. Recently, ripasudil hydrochloride hydrate, a selective Rho-associated protein kinase inhibitor, was launched for the treatment of glaucoma. However, adverse events, such as conjunctival hyperemia, are often noted in clinical trials using healthy subjects. Therefore, we investigated the onset, offset, and kinetic changes of conjunctival hyperemia induced by ripasudil ophthalmic solution in patients with open-angle glaucoma or ocular hypertension who had already been treated with anti-glaucoma eye drops other than ripasudil. Conjunctival hyperemia was evaluated by both clinical grading by 3 ophthalmic physicians and pixel coverage of conjunctival blood vessels determined by conjunctival hyperemia-analyzing software. Conjunctival hyperemia appeared within 10 min post-instillation in most of the participants. Clinical grade and pixel coverage increased significantly 10 min post-instillation and then decreased. In most of the participants, hyperemia resolved within 2 h. Median conjunctival hyperemia offset was 90 min. A tendency of monotonic increase was observed between clinical grade and pixel coverage. Taken altogether, hyperemia induced by ripasudil was transient in glaucoma patients who had already been treated with anti-glaucoma eye drops other than ripasudil.

Topics: Adult; Aged; Aged, 80 and over; Case-Control Studies; Conjunctival Diseases; Female; Glaucoma, Open-Angle; Humans; Hyperemia; Isoquinolines; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Prospective Studies; Sulfonamides; Young Adult

To investigate the intra-ocular pressure (IOP)-lowering effects and safety of 0.4% ripasudil (K-115), a Rho kinase inhibitor, twice daily for 52 weeks, in patients with open-angle glaucoma or ocular hypertension (OHT).. In this multicentre, prospective, open-label study, 388 patients with primary open-angle glaucoma, OHT or exfoliation glaucoma were enrolled and 354 of them were subdivided into four cohorts (monotherapy, 173; additive therapy to prostaglandin analogs, 62; β-blockers, 60; or fixed combination drugs, 59). The IOP reduction at trough and peak from baseline and adverse events was investigated.. Ripasudil showed IOP-lowering effects over 52 weeks in all the analyses of monotherapy, additive therapy and both subgroups (baseline IOP ≥21 mmHg and <21 mmHg) of monotherapy. The mean IOP reductions at trough and peak at week 52 were -2.6 and -3.7 mmHg for monotherapy, and -1.4 and -2.4, -2.2 and -3.0, and -1.7 and -1.7 mmHg, respectively, for additive therapy described above. The most frequently observed adverse events were conjunctival hyperaemia (n = 264, 74.6%), blepharitis (n = 73, 20.6%) and allergic conjunctivitis (n = 61, 17.2%). Most of the conjunctival hyperaemia findings were mild (97.0%), transient and resolved spontaneously (78.0%). Although 51 patients discontinued from the study due to blepharitis and/or allergic conjunctivitis (blepharitis, 28; allergic conjunctivitis, 17; both, 6), all the events resolved with or without treatment after the discontinuation of ripasudil administration.. Fifty-two week administration of 0.4% ripasudil revealed IOP-lowering effects and an acceptable safety profile when administered as monotherapy or as additive therapy, in patients with open-angle glaucoma or OHT.

Topics: Adrenergic beta-Antagonists; Aged; Antihypertensive Agents; Drug Combinations; Female; Follow-Up Studies; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Isoquinolines; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Prospective Studies; rho-Associated Kinases; Sulfonamides; Tonometry, Ocular

To investigate the intra-ocular pressure (IOP)-lowering effects of a selective Rho kinase inhibitor, ripasudil (K-115), over 24 hr in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT).. In this multicenter, prospective, randomized, open-label, 3-period, Latin-square crossover clinical study, 28 patients with POAG or OHT whose IOP level was 21 mmHg or higher were subdivided into three groups. Each patient was treated with placebo and ripasudil in concentrations of 0.2 and 0.4%, at 9:00 and 21:00 on day 1 through a total of 3 periods separated by washout periods. IOP was measured at 9:00, 10:00, 11:00, 13:00, 16:00, 19:00, 21:00, 22:00 and 23:00 on day 1, and 1:00, 4:00, 7:00 and 9:00 on day 2 in sitting position using Goldmann applanation tonometer. Main outcome measure was the IOP reduction of placebo and ripasudil from baseline.. The mean IOP reduction was -5.2 mmHg for 0.2%, -6.4 mmHg for 0.4% and -2.0 mmHg for placebo at 2 hr after the first instillation. Also, the corresponding values were -6.8 mmHg for 0.2%, -7.3 mmHg for 0.4% and -4.1 mmHg for placebo at 2 hr after the second instillation. Statistically significant IOP reduction, compared with placebo, was found for both 0.2 and 0.4% from 1 through 7 hr after each instillation. In safety, conjunctival hyperaemia was observed in 22 patients (79%) for 0.2%, 27 patients (96%) for 0.4% and three patients (11%) for placebo.. Ripasudil is a promising new topical medication to lower IOP for at least 7 hr after instillations in patients with POAG or OHT.

Topics: Adult; Circadian Rhythm; Cross-Over Studies; Enzyme Inhibitors; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Isoquinolines; Male; Middle Aged; Ocular Hypertension; Prospective Studies; rho-Associated Kinases; Sulfonamides; Tonometry, Ocular

Ripasudil hydrochloride hydrate (K-115), a novel rho kinase inhibitor, provides statistically significant intraocular pressure (IOP)-lowering effects and has a tolerable safety profile. However, no studies have evaluated ripasudil combined with β-blockers and prostaglandin analogues.. To evaluate the additive IOP-lowering effects and the safety of ripasudil, 0.4%, combined with timolol, 0.5%, or latanoprost, 0.005%, in patients with primary open-angle glaucoma or ocular hypertension.. We conducted 2, multicenter, randomized, double-masked, parallel group comparison studies of ripasudil-timolol and ripasudil-latanoprost in 29 and 36 Japanese clinical centers, respectively. Analyses were performed on an intention-treat-treat basis. After appropriate run-in periods with timolol or latanoprost, 208 and 205 patients whose IOP levels were 18 mm Hg or higher were enrolled in the ripasudil-timolol and ripasudil-latanoprost groups, respectively. Enrollment began December 1, 2011, and follow-up was completed on September 7, 2012, in the ripasudil-timolol study. Enrollment began December 1, 2011, and follow-up was completed on September 27, 2012, in the ripasudil-latanoprost study.. Patients were subdivided into 2 groups in each study and were treated with ripasudil or placebo twice daily for 8 weeks.. The IOP reductions in the ripasudil and placebo groups were analyzed with a repeated-measures analysis of variance model at weeks 4, 6, and 8, at trough (before instillation [9 am]) and peak (2 hours after instillation [11 am]) levels.. In the ripasudil-timolol study, the mean IOP reductions from baseline in the ripasudil and placebo groups were -2.4 and -1.5 mm Hg at 9 am for a difference of 0.9 mm Hg (95% CI, 0.4-1.3 mm Hg; P < .001) and -2.9 and -1.3 mm Hg at 11 am for a difference of 1.6 mm Hg (95% CI, 1.1-2.1 mm Hg; P < .001), respectively. In the ripasudil-latanoprost study, those IOP reductions were -2.2 and -1.8 mm Hg at 9 am for a difference of 0.4 mm Hg (95% CI, -0.0 to 0.9 mm Hg; P = .06) and -3.2 and -1.8 mm Hg at 11 am for a difference of 1.4 mm Hg (95% CI, 0.9-1.9 mm Hg; P < .001), respectively. The most frequently reported adverse event was conjunctival hyperemia, which was mild and in most cases resolved without treatment before the next instillation.. These clinical trials found additive IOP-lowering effects of ripasudil from placebo at trough and peak levels in combination with timolol and at peak level in combination with latanoprost. However, a definitive difference in the addition of placebo to latanoprost was not identified in the trough level.. clinicaltrials.jp Identifiers: JAPIC111700 and JAPIC111701.

Topics: Aged; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Glaucoma, Open-Angle; Humans; Isoquinolines; Japan; Latanoprost; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Prostaglandins F, Synthetic; rho-Associated Kinases; Severity of Illness Index; Sulfonamides; Time Factors; Timolol; Tonometry, Ocular; Treatment Outcome

To identify the optimal dose of a novel Rho kinase inhibitor, K-115, by assessing dose dependency of the intraocular pressure (IOP)-lowering effects and the safety in patients with primary open-angle glaucoma or ocular hypertension.. Multicenter, prospective, randomized, placebo-controlled, double-masked, parallel group comparison clinical study.. After appropriate washout periods, 210 patients with primary open-angle glaucoma or ocular hypertension were subdivided into 4 groups and were treated with K-115 in concentrations of 0.1%, 0.2%, and 0.4% or placebo twice daily for 8 weeks. The dose response of IOP reduction and the incidence of adverse events by K-115 or placebo were investigated.. The mean baseline IOP was between 23.0 and 23.4 mm Hg. The mean IOP reductions of the last visit from baseline were -2.2 mm Hg, -3.4 mm Hg, -3.2 mm Hg, and -3.5 mm Hg, respectively, in the placebo, 0.1%, 0.2%, and 0.4% groups at before instillation (9:00); -2.5 mm Hg, -3.7 mm Hg, -4.2 mm Hg, and -4.5 mm Hg at 2 hours after instillation (11:00); and -1.9 mm Hg, -3.2 mm Hg, -2.7 mm Hg, and -3.1 mm Hg at 8 hours after instillation (17:00). The dose-dependent IOP-lowering effect of K-115 was statistically significant at all time points. Also, conjunctival hyperemia was found in 7 (13.0%) of 54 patients for placebo, 23 (43.4%) of 53 patients for the 0.1% group, 31 (57.4%) of 54 patients for the 0.2% group, and 32 (65.3%) of 49 patients for the 0.4% group.. On the basis of this dose-response study, K-115 0.4% has been selected to be the optimal dose and has the potential to be a promising new agent for glaucoma to control 24-hour IOP by twice-daily dosing.

Topics: Antihypertensive Agents; Dose-Response Relationship, Drug; Double-Blind Method; Enzyme Inhibitors; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Isoquinolines; Male; Middle Aged; Ocular Hypertension; Prospective Studies; rho-Associated Kinases; Sulfonamides; Tonometry, Ocular

Ripasudil is a class of drug which alters the trabecular meshwork to increase the aqueous outflow and has been shown to be effective in pseudoexfoliative glaucoma (PXF G). This study aimed at assessing the efficacy and safety profile of ripasudil as an adjunct treatment in patients with PXF G at maximal tolerated antiglaucoma medications.. In this prospective, interventional study, 40 patients with PXF G were enrolled between May 2021 and Jan 2022. Ripasudil 0.4% was started as an adjunctive drug to the ongoing antiglaucoma medications. On follow-up visits at 1, 3, and 6 months, the visual acuity, intraocular pressure (IOP), anterior segment, and fundus findings were evaluated. The premedication and postmedication IOP values were compared by paired t-test, and a P-value <0.05 was considered statistically significant.. Average age at recruitment was 60.02 ± 8.74 years. Baseline premedication IOP was 25.375 ± 3.276 mmHg. IOP reduction at 6 months was found to be statistically significant in all patients, with the maximal response being 24.13%. Also, 87.5% (35/40) of patients reached target IOP or even lower IOP at the end of study. There was no statistically significant association between the PXF grade and IOP. However, the grade of inferior iridocorneal angle pigmentation was found to be higher in eyes with elevated IOP (P < 0.05). Only three patients developed conjunctival hyperemia as an adverse reaction, which was mild and transient.. Ripasudil showed additional IOP-lowering effect with other antiglaucoma medications and exhibited no significant side effects.

Topics: Aged; Antiglaucoma Agents; Glaucoma; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Middle Aged; Ophthalmic Solutions; Prospective Studies; rho-Associated Kinases; Treatment Outcome

This study investigated the effects of dexamethasone (Dex) on human trabecular meshwork (TM) cells, a model of glucocorticoid-induced glaucoma, and evaluated the impact of ripasudil (Rip) as a co-delivery or sequential dosing strategy.. In vitro experiments were conducted to assess the effects of Dex and Rip on TM cells. Confocal microscopy was used to evaluate the impact of Dex and Rip on F-actin staining signals. Contractility of the TM cells upon Dex and Rip treatment mimicking co-delivery and sequential delivery was quantified using collagen gel contraction assay. Transepithelial electrical resistance (TEER) values and fluorescein isothiocyanate (FITC)-dextran permeability were also measured to assess the impact of Dex and Rip on TM cells.. Dex and Rip did not exhibit cytotoxicity at the maximum tested concentration (20 µM). Dex-treated TM cells exhibited higher F-actin staining signals compared to controls, which were reduced when co-treated with Rip. Rip inhibited Dex-induced collagen gel contraction activity in both co-delivery and sequential treatments. Dex resulted in increased TEER values as the dose increased, whereas TEER values were maintained when co-treated with Rip.. Co-delivery of Rip has the potential to prevent glaucoma symptoms when patients are treated with Dex. This study highlights the importance of identifying strategies to reduce the side effects of prolonged use of glucocorticoids, such as Dex, in the treatment of various diseases.. This study demonstrates the potential of co-delivering ripasudil with dexamethasone to mitigate glucocorticoid-induced ocular hypertension and a secondary glaucoma that resembles primary open-angle glaucoma, providing insights for the development of novel preventive strategies in clinical care.

Topics: Actins; Collagen; Dexamethasone; Glaucoma; Glaucoma, Open-Angle; Glucocorticoids; Humans; Phenotype; rho-Associated Kinases; Trabecular Meshwork

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.. 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. The primary safety endpoint was the incidence of adverse drug reactions (ADRs) (including blepharitis, plus assessment of its background factors); the primary efficacy endpoint was change in intraocular pressure (IOP) from baseline to 24 months.. A total of 3374 Japanese patients with glaucoma or ocular hypertension were evaluated for safety and 3178 for effectiveness of ripasudil over a mean 524.5-day observational period. Overall, 853 (25.3%) patients experienced adverse drug reactions; the most common were blepharitis (8.6%), conjunctival hyperemia (8.5%), and conjunctivitis (6.3%). Multivariate analyses demonstrated that patients were more likely to experience the ADR blepharitis with ripasudil treatment if they were female (hazard ratio [HR] 1.307; p = 0.040), had comorbid or a previous history of blepharitis (HR 2.178; p = 0.001), or had a history of allergy to pollen (HR 1.645; p = 0.003) or medication (HR 2.276; p < 0.001). IOP decreased significantly from baseline with ripasudil; the least-squares mean ± standard error change in IOP from baseline to 24 months was - 2.6 ± 0.1 mmHg (p < 0.001). Significant IOP changes were seen in four types of glaucoma, namely primary open-angle glaucoma, normal-tension glaucoma, primary angle-closure glaucoma, and secondary glaucoma, and ocular hypertension.. Ripasudil was safe and effective as an antiglaucoma medication with no new safety signals identified and significant reductions in IOP maintained over 24 months of treatment.

Topics: Antihypertensive Agents; Blepharitis; Drug-Related Side Effects and Adverse Reactions; Female; Glaucoma; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Isoquinolines; Ocular Hypertension; Ophthalmic Solutions; Prospective Studies; rho-Associated Kinases; Sulfonamides; Treatment Outcome

To investigate the time-dependent change of corneal endothelial cell (CEC) morphology and density (CECD) in patients with glaucoma post instillation of rho-associated protein kinase inhibitor ripasudil (Rip) 0.4% eye drops.. This observational study involved 163 eyes of 163 patients with glaucoma in whom CEC morphological change was evaluated by CECD calculated via non-contact specular microscopy (NCSM) before and at 1 or 3 months post-Rip instillation. The change of CECD was plotted along with elapsed time from last instillation of Rip. The patients were divided into the following three groups based on the elapsed time post-Rip instillation: Early Group (<2 hours), Middle Group (≥2 hours, yet <6 hours) and Late Group (≥6 hours). The rate of CECD change was then analysed and compared among the three groups. An additional eight eyes of four patients with glaucoma were enrolled for a time-dependent study, with NCSM images evaluated before and at 1, 2, 3, 4 and 6 hours post-Rip instillation.. Morphological changes in the CECs appeared within 1 hour and recovered to normal within 6 hours post instillation. In the Early, Middle and Late Group, the median rate of CECD change as calculated by the NCSM automated software was -5.68%, -4.95% and -0.07%, respectively. The CEC images showed the same morphological changes with observational study in all four cases.. Due to transient morphological changes, the NCSM software produced misleading data for determining CECD within 1 hour post-Rip instillation, yet revealed that CEC morphology gradually recovered to normal within 6 hours.

Topics: Administration, Ophthalmic; Aged; Aged, 80 and over; Cell Count; Endothelium, Corneal; Enzyme Inhibitors; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Isoquinolines; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Recovery of Function; Retrospective Studies; rho-Associated Kinases; Sulfonamides; Time Factors

To compare the intraocular pressure (IOP)-lowering effects of ripasudil, a rho-kinase inhibitor, and selective laser trabeculoplasty (SLT) as adjuvant therapy in Japanese glaucoma patients and to identify the factors associated with treatment success.. We performed a retrospective medical chart review of patients with glaucoma who received ripasudil or SLT as an adjuvant therapy. We collected data on 65 eyes (65 patients) with primary open-angle glaucoma, normal-tension glaucoma, or exfoliation glaucoma with at least 12 months of follow-up. IOP and number of glaucoma medications at 0, 1, 3, 6, 9, and 12 months were compared between and within groups. A repeated-measures mixed model was used to perform statistical analysis. We also investigated factors associated with treatment success, which was defined as ≥ 20% reduction in IOP at all follow-up periods, using univariate and multivariate logistic regression analysis.. Significant IOP reduction was observed at all time-points after treatment in the ripasudil group (n = 33) and in the SLT group (n = 32), with no statistically significant difference between the groups before or after treatment. Patients in the SLT group used more anti-glaucoma medications before treatment, but fewer during follow-up, than those in the ripasudil group. Regardless of treatment, higher baseline IOP was associated with treatment success [crude odds ratio: 1.21 (95% confidence interval: 1.06-1.38), adjusted odds ratio: 1.37 (95% confidence interval: 1.06-1.77)].. Adjuvant SLT or ripasudil in patients with inadequately controlled glaucoma both reduced IOP to a similar degree, but SLT contributed to reducing the number of medications used.

Topics: Glaucoma; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Isoquinolines; Laser Therapy; Lasers; Retrospective Studies; rho-Associated Kinases; Sulfonamides; Trabeculectomy; Treatment Outcome

We examined responsiveness to ripasudil as a potential factor for predicting the effect of selective laser trabeculoplasty (SLT) when performed for primary open-angle glaucoma (POAG). A total of 70 eyes with no history of glaucoma surgery underwent SLT between January 2015 and June 2019. Patients were divided into two groups, with an intraocular pressure (IOP) decrease of 15% or more due to ripasudil administration before SLT defined as the effective group, while an IOP decrease of less than 15% was defined as the non-effective group. Kaplan-Meier survival analysis was performed. A Cox proportional hazards model assessed the influence of baseline factors on the success. Of the 70 eyes evaluated, treatments were effective in 22 and non-effective in 48. Postoperatively, both groups exhibited IOP reductions for up to 24 months. Success ratios at 12 and 24 months after SLT were 43.5% and 18.5% in the effective versus 24.9% and 9.3% in the non-effective group, which were significantly higher in the effective group (P = 0.03). Presence of a ripasudil effective eye (P = 0.03) was associated with treatment success. Responsiveness to ripasudil may be useful in predicting the therapeutic effect of SLT.

Topics: Aged; Aged, 80 and over; Female; Glaucoma, Open-Angle; Humans; Isoquinolines; Kaplan-Meier Estimate; Laser Therapy; Male; Protein Kinase Inhibitors; Retrospective Studies; Sulfonamides; Trabeculectomy; Treatment Outcome

Topics: Aged; Blepharitis; Conjunctival Diseases; Female; Glaucoma, Open-Angle; Humans; Hyperemia; Intraocular Pressure; Isoquinolines; Japan; Male; Middle Aged; Ophthalmic Solutions; Retrospective Studies; rho-Associated Kinases; Safety; Sulfonamides; Treatment Outcome

To elucidate molecular pharmacology of Rho-associated coiled-coil containing protein kinase inhibitors (ROCK-i, Ripasudil and Y27632) on their efficiency for aqueous outflow, 2D or 3D cultures of a human trabecular meshwork (HTM) were prepared in the presence of TGFβ2. Those were examined by transendothelial electrical resistance (TEER, 2D), electronic microscopy (EM, 2D and 3D), expression of the extracellular matrix (ECM) including collagen1 (COL1), COL4 and COL6, and fibronectin (FN) by immunolabeling and/or quantitative PCR (3D), and solidity of 3D organoids by a micro-squeezer. TGFβ2 significantly increased the TEER values in 2D cultures, and the ECM expression indicated that the 3D organoids assumed a more densely packed shape. ROCK-i greatly reduced the TGFβ2-induced enhancement of TEER and the immunolabeled ECM expression of the 3D organoids. In contrast, the mRNA expression of COL1 was increased, and those of COL4 and FN were unchanged. EM revealed that TGFβ2 caused the HTM cells to become more compact and abundant ECM deposits within the 3D organoids were observed. These were significantly inhibited by ROCK-i. The dense solids caused by the presence of TGFβ2 were significantly suppressed by ROCK-i. Current study indicates that ROCK-i cause beneficial effects toward the spatial configuration of TGFβ2-induced HTM 3D organoids.

Topics: Amides; Antihypertensive Agents; Cell Culture Techniques; Cell Line; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Isoquinolines; Microscopy, Electron, Scanning; Optic Nerve Diseases; Organoids; Pyridines; rho-Associated Kinases; Spheroids, Cellular; Sulfonamides; Trabecular Meshwork; Transforming Growth Factor beta2

To investigate morphological changes in type VI collagen in the human trabecular meshwork associated with the rho kinase inhibitor ripasudil.. This cross-sectional study evaluated the effects of ripasudil eye drop administration (RA) or no ripasudil eye drop administration (NRA) in patients with primary open-angle glaucoma (POAG; age range 60-80 years) who underwent conventional outflow reconstruction between December 2015 and September 2016 at Tokai University Hachioji Hospital. The juxtacanalicular tissue was removed and imaged using transmission electron microscopy. Type VI collagen comprises cross-banded aggregates with transverse bands 30 nm apart repeating every 105 nm. The transverse bands are called the outer rod-like region (ORR) and the intervals are called the inner rod-like region (IRR). The waveform intensity in the type VI collagen was analysed in electron micrographs using Fourier transformation to detect the IRR and ORR borders.. Ten eyes of 10 patients were included (n=5/group). The baseline characteristics did not differ significantly between groups. ORR width was significantly smaller in the RA group (37.85±3.43 nm) than in the NRA group (50.62±5.23 nm, p<0.05), whereas IRR width was significantly greater in the RA group (70.68±10.84 nm) than in the NRA group (58.19±5.34 nm, p<0.05). Morphological changes in the type VI collagen total width tended to correlate with the duration of ripasudil administration (r=0.9, p=0.08).. Ripasudil administration in patients with POAG induced morphological changes in type VI collagen. Patients with POAG administered RA had a significantly smaller ORR width and a significantly greater IRR width than patients with POAG not administered RA.

Topics: Aged; Aged, 80 and over; Biomarkers; Collagen Type VI; Cross-Sectional Studies; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Isoquinolines; Male; Middle Aged; Ophthalmic Solutions; Retrospective Studies; rho-Associated Kinases; Sulfonamides; Trabecular Meshwork

To examine the use of ripasudil as a trabeculotomy outcome marker in patients with primary open-angle glaucoma (POAG).. Between May 2015 and December 2018, 35 eyes underwent trabeculotomy and were postoperatively followed for over 3 months. Ripasudil was defined as effective if drug administration resulted in a greater than 10% reduction in intraocular pressure (IOP). Patients were divided into effective (effective group) or non-effective (non-effective group) ripasudil administration groups. The need for additional glaucoma surgery or an IOP ≥ 21 mmHg indicated surgical failure. In both groups, a Kaplan-Meier survival-analysis was used to evaluate success probabilities related to postoperative IOP levels.. Effective IOP reduction occurred in 14 of 35 eyes after ripasudil administration, which was shown by a decrease of more than 10%. Postoperatively, both groups exhibited significant reductions of IOP and antiglaucoma medication use for up to 24 months. At 12 and 24 months after trabeculotomy, probabilities of success in the effective vs. non-effective group were 100% vs. 94.7 and 100% vs. 75.4%, respectively (P = 0.14).. Trabeculotomy is effective for achieving an IOP < 21 mmHg in ripasudil effective POAG eyes. Examination of ripasudil's IOP-lowering effects may be useful in predicting surgical outcomes after trabeculotomy.

Topics: Adult; Aged; Enzyme Inhibitors; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Isoquinolines; Kaplan-Meier Estimate; Middle Aged; Ocular Hypertension; Retrospective Studies; rho-Associated Kinases; Sulfonamides; Trabeculectomy

To evaluate the safety and intraocular pressure (IOP)-lowering effects of a ripasudil 0.4% ophthalmic solution in Japanese patients with glaucoma and ocular hypertension (OH) as a post-marketing surveillance.. This was a 2-year prospective observational study in patients with glaucoma or OH who had not previously received ripasudil. Patients registered in the study using a central internet-based system from June 1, 2015 to April 30, 2017. Data on adverse drug reactions (ADRs) and IOP were collected and analysed from the first 3 months of ripasudil treatment.. Of the 3058 patients in the safety analysis set, 3016 had IOP data and were included in the efficacy analysis. ADRs were seen in 244 (8.0%) of the 3058 patients. IOP decreased significantly in patients with primary open-angle glaucoma (- 2.9 ± 4.2 mmHg; p < 0.001), normal tension glaucoma (- 1.7 ± 2.4 mmHg; p < 0.001), primary angle-closure glaucoma (- 3.9 ± 5.3 mmHg; p < 0.001), and OH (- 3.8 ± 5.8 mmHg; p < 0.001). Significant IOP reduction was also noted in exfoliation glaucoma (- 3.0 ± 5.5 mmHg; p < 0.001), uveitis-associated glaucoma (- 4.7 ± 7.2 mmHg; p < 0.001) and steroid glaucoma (- 5.5 ± 6.0 mmHg; p < 0.001), but not for neovascular glaucoma (- 2.8 ± 12.1 mmHg; p = 0.669).. Ripasudil was safe and effective in the treatment of glaucoma and OH in Japanese patients, with a low incidence of ADRs or treatment discontinuation, and reduced IOP after 3 months of treatment.. Kowa Company, Ltd., Tokyo, Japan.

Topics: Aged; Dose-Response Relationship, Drug; Female; Glaucoma; Glaucoma, Open-Angle; Humans; Incidence; Intraocular Pressure; Isoquinolines; Japan; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Product Surveillance, Postmarketing; Prospective Studies; Sulfonamides; Tonometry, Ocular; Treatment Outcome

Blepharitis was the most common side effect leading to discontinuation of ripasudil therapy. Prior allergic reactions to other topical glaucoma were found to be a risk factor for ripasudil-induced blepharitis.. To report the incidence proportion of blepharitis and its relating factors due to long-term use of 0.4% riapasudil, a Rho-kinase inhibitor, in glaucoma patients of a clinical setting.. One hundred three eyes of 103 consecutive glaucoma patients who started ripasudil treatment between December 2014 and February 2017 at our institute, and who had a follow-up period of over 6 months were enrolled in this study. Incidence proportion, time required for recovery and risk factors associated with blepharitis and other side effects that led to discontinuation of ripasudil treatment were considered.. The most frequently observed side effect was blepharitis (25.2%). The 12- and 24-month discontinuation rate due to blepharitis was 21.1%±8.2% and 34.6%±11.8% (average±SE), respectively (Kaplan-Meier analysis). Most patients recovered from blepharitis symptoms within 4 weeks, but 5 patients required over 8 weeks for recovery. Past history of allergic reactions to other topical glaucoma medication was significantly correlated with the manifestation of blepharitis (Cox proportional hazard model, P<0.007) while age, sex, intraocular pressure reduction rate, number of administered eye drops, history of systemic allergic diseases were not.. Blepharitis was the most common reason for discontinuation of ripasudil treatment. Although most cases were resolved spontaneously, prolonged blepharitis was observed in a few patients. A past history of allergic reaction to other glaucoma medication indicates a higher possibility of blepharitis with ripasudil use and warrants careful administration.

Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Blepharitis; Edema; Erythema; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Isoquinolines; Male; Middle Aged; Ophthalmic Solutions; Ophthalmoscopy; rho-Associated Kinases; Sulfonamides

The current study aimed to address whether ripasudil, a Rho-associated coiled-coil containing protein kinase (ROCK) inhibitor developed to treat glaucoma and ocular hypertension (OH), improves diabetic macular edema (DME) since it is known that ROCK upregulates vascular endothelial growth factor. We retrospectively investigated the foveal thickness (FT) measured by spectral-domain optical coherence tomography, visual acuity (VA), and intraocular pressure (IOP) in 12 eyes with DME that received ripasudil treatment for primary open-angle glaucoma or OH and compared them with 14 eyes that received no treatment. One month after ripasudil therapy, the mean FT decreased significantly from 439 ± 72 µm to 395 ± 62 µm (P = 0.003); this change was significantly different from that in the controls, in which the mean FT increased by 1 ± 39 µm (P = 0.01). Ripasudil also caused a significant decrease in IOP from 17.3 ± 5.2 mmHg to 14.6 ± 4.0 mmHg (P = 0.02); this change was significantly greater than that in the controls, in which IOP changed by 0.0 ± 1.6 mmHg (P < 0.008). There was no significant difference in the VA changes between groups. Our results suggested that ripasudil may have positive effects on both IOP and DME.

Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Diabetes Complications; Diabetes Mellitus; Diabetic Retinopathy; Female; Glaucoma; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Isoquinolines; Macular Edema; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Retrospective Studies; rho-Associated Kinases; Sulfonamides; Tomography, Optical Coherence; Visual Acuity

The purpose of this study was to describe the initial experience, efficacy, and safety of ripasudil hydrochloride hydrate (ripasudil), a Rho-associated kinase inhibitor eye drop, for uveitic glaucoma.. In this retrospective case series, we retrieved the clinical data of 21 eyes from 19 patients with open-angle uveitic glaucoma who were treated with ripasudil at Kobe University Hospital. We analyzed the median intraocular pressure (IOP) reductions after ripasudil treatment and collected the information on the adverse events that were encountered during the course of this treatment period.. The causes of uveitis were sarcoidosis (29%), Behçet's disease (14%), Vogt-Koyanagi-Harada disease (10%), others (15%), and unclassified (33%). Of total, 19 (90%) eyes were treated with topical, periocular, and/or systemic steroid therapies. The median number of glaucoma medications used before ripasudil treatment was 2, and the median follow-up time was 13 months. The median IOPs were 23 mmHg at baseline, 16 mmHg at 1 month, and 18 mmHg at 12 months with significant IOP reductions of - 3 mmHg at 1 month and - 2 mmHg at 12 months (P = 0.0050). Of total, 11 (52%) eyes with an IOP reduction ≥ 3 mmHg at 1 month (responders) showed a significant median IOP decrease at 12 months compared with non-responders (- 5 versus 0 mmHg, P = 0.0242). Two adverse events were observed: rashes on the back and transient conjunctival hyperemia.. Ripasudil appears to be safe and substantially reduce IOP in eyes with uveitic glaucoma if the eye is a responder. Ripasudil could be an option for the treatment of uveitic glaucoma.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Dose-Response Relationship, Drug; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Isoquinolines; Male; Middle Aged; Ophthalmic Solutions; Retrospective Studies; rho-Associated Kinases; Sulfonamides; Treatment Outcome; Young Adult

To assess the responses of the superficial peripapillary retinal vessel density (VD) and prelaminar flow index (PLFI) to topical Rho-assisted coiled-coil forming protein kinase (ROCK) inhibitor ripasudil and alpha-2 agonist brimonidine using optical coherence tomography angiography.. This is a prospective, non-randomized, comparative cohort study. We studied the response of optical coherence tomography angiography (OCTA) parameters to drugs in 24 eyes treated with ripasudil and 23 eyes treated with brimonidine at the Sensho-kai Eye Institute. After division by the signal strength (SS), we compared the responses of peripapillary VD/SS and PLFI/unit area (UA)/SS to topical eye drops in eyes with primary open-angle glaucoma (POAG) and ocular hypertension (OH).. In the superficial peripapillary retina, VD/SS increased significantly in the ripasudil-treated eyes (12.5 ± 21.7%, P = 0.018), but not in the brimonidine-treated eyes (- 2.0 ± 13.8%, P = 0.484). In the deeper area of the optic disc, the changes in the PLFI/UA/SS in the brimonidine-treated eyes (+ 0.9 ± 8.9%, P = 1.00) and ripasudil-treated eyes (- 1.3 ± 8.5%, P = 0.241) were not significant. Multivariate discriminant analysis showed that the change in the peripapillary VD/SS was the most important parameter (P = 0.0186) for differentiating ripasudil- and brimonidine-treated eyes.. The topical ROCK inhibitor ripasudil enhanced the peripapillary VD in POAG and OH, whereas the alpha-2 agonist brimonidine did not. The PLFI did not respond to either drug.

Topics: Adrenergic alpha-2 Receptor Agonists; Aged; Brimonidine Tartrate; Dose-Response Relationship, Drug; Female; Fluorescein Angiography; Follow-Up Studies; Fundus Oculi; Glaucoma, Open-Angle; Humans; Instillation, Drug; Intraocular Pressure; Isoquinolines; Male; Middle Aged; Ocular Hypertension; Optic Disk; Prospective Studies; Retinal Vessels; rho-Associated Kinases; Sulfonamides; Tomography, Optical Coherence

To compare the effectiveness and safety of either switching from topical prostaglandin (PG) analog monotherapy to topical PG/timolol fixed combination therapy or adding topical ripasudil therapy.. An open-label, prospective, randomized, parallel group, comparative study METHODS: Fifty-one patients (51 eyes) with primary open-angle glaucoma who experienced insufficient intraocular pressure (IOP) control while taking a PG analog were enrolled. The participants were divided into the following treatment groups: PG/timolol fixed combination (switched group) or ripasudil therapy addition (added group). Blood pressure, IOP, and pulse rate were measured at baseline and after 1 and 3 months of study treatment. Adverse reactions and decreased effectiveness were examined.. The mean IOP after 3 months of therapy was 14.3 ± 2.2 mmHg in the switched group and 14.7 ± 3.0 mmHg in the added group, both of which were significantly lower than those at baseline (switched, 16.3 ± 3.0 mmHg; added, 16.6 ± 2.8 mmHg; both P < .001). At 3 months, the IOP was reduced by 2.0 ± 1.7 mmHg (11.7 ± 9.6%) in the switched group and by 1.8 ± 2.1 mmHg (10.7 ± 12.5%) in the added group. In the added group, the diastolic blood pressure after 1 month of therapy was significantly lower than that at baseline (P < .05). In the switched group, 10 (40.0%) and 2 (8.0%) participants experienced adverse reactions at 1 and 3 months, respectively. In the added group, 6 (23.1%) and 4 (15.4%) participants experienced adverse reactions at 1 and 3 months, respectively. Treatment was discontinued in 4 participants (16.0%) in the switched group and in 1 participant (3.8%) in the added group.. Treatment changes involving either switching from a PG analog to PG/timolol fixed combination eye drops or adding ripasudil to PG analog therapy were equally safe and effective in reducing IOP.

Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Dose-Response Relationship, Drug; Drug Substitution; Drug Therapy, Combination; Female; Follow-Up Studies; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Isoquinolines; Male; Middle Aged; Ophthalmic Solutions; Prospective Studies; Prostaglandins F, Synthetic; rho-Associated Kinases; Sulfonamides; Timolol; Treatment Outcome

Ripasudil accelerates aqueous humour drainage along the trabecular meshwork-Schlemm's canal route and has been approved for clinical use in Japan. We retrospectively investigated the efficacy and safety of adding ripasudil to existing treatment regimens to reduce intraocular pressure (IOP) in patients with glaucoma.. A total of 119 eyes from 119 subjects (61 men, 58 women) with primary open-angle glaucoma or ocular hypertension who had ripasudil added to their treatment regimens between December 2014 and June 2015 were included. An average of 3.8 ± 1.0 anti-glaucoma medications was in use before adding ripasudil. Subjects were divided into four groups based on the number of medications included in the original treatment regimen: ≤2, 3, 4, or ≥5 medications. The IOP was compared before and after 1 and 3 months of treatment with ripasudil for all subjects and between groups. Patients for whom ripasudil use was discontinued within 3 months were also examined.. The IOP was significantly lower in all patients after 1 month (17.5 ± 4.5 mmHg) and 3 months (16.8 ± 4.2 mmHg) of treatment than it was before (19.8 ± 5.3 mmHg, p < 0.0001). All groups were equivalent in the rate and magnitude of IOP change. Ripasudil administration was discontinued in five patients (4.2%) prior to the end of the study: three were lost to follow-up and two underwent glaucoma surgery.. Adding ripasudil to existing glaucoma treatment regimens is effective and safe in reducing IOP, regardless of the number of medications in use.

Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Isoquinolines; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Retrospective Studies; Sulfonamides

The aim of this study was to evaluate the one-year efficacy, ability to lower intraocular pressure, and tolerability of ripasudil, a rho-kinase inhibitor, in patients with glaucoma inadequately controlled with maximum medical therapy.. This prospective, non-comparative, interventional case-series study included 39 patients with primary open-angle glaucoma inadequately controlled with maximum medical therapy before treatment with ripasudil. Ripasudil was administered twice per day as adjunctive therapy to ongoing glaucoma treatment. The primary endpoint was the degree of intraocular pressure reduction after 12 months of treatment; the secondary endpoints were the incidence of adverse events.. We examined 39 eyes. The intraocular pressure reduction (given as the relative percentage of intraocular pressure reduction) from baseline was -2.6 mmHg (-15.5%; 95% confidence interval, -1.1 to -3.9 mmHg; P < 0.001) after 12 months of treatment. The adverse events were conjunctival hyperemia (all patients), blepharitis (three), allergic conjunctivitis (two), punctate keratitis (two), and ophthalmalgia (one).. Treatment with ripasudil decreased intraocular pressure in patients with glaucoma that was poorly controlled with maximal medical therapy, and it was well-tolerated.

Topics: Adult; Aged; Antihypertensive Agents; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Isoquinolines; Male; Middle Aged; Ophthalmic Solutions; Prospective Studies; rho-Associated Kinases; Sulfonamides; Time Factors; Tonometry, Ocular; Treatment Outcome; Young Adult

The purpose of the study was to evaluate the intraocular pressure (IOP)-lowering effect and tolerability of ripasudil, a rho-kinase inhibitor, in patients with glaucoma inadequately controlled with maximum medical therapy.. This prospective, noncomparative, interventional case series study included 35 patients with primary open angle glaucoma, in whom the glaucoma was poorly controlled with maximum medical therapy before starting the treatment with ripasudil. Ripasudil was instilled twice a day as adjunctive therapy to the ongoing glaucoma treatment. The primary end point was the degree of IOP reduction after 3 months of treatment, whereas the secondary end points were the percentage of patients reaching the predefined target IOP and the incidence of adverse events.. We examined 35 eyes of 35 patients with primary open angle glaucoma. The IOP reduction (relative percentage IOP reduction) from baseline was -2.8 mm Hg (-15.5%; 95% confidence interval, -1.6 to -3.9 mm Hg; P<0.001) after 3 months of treatment. The predefined target IOP was achieved in 48.5% (17/35) of the patients. The adverse events were conjunctival hyperemia (all patients), allergic conjunctivitis (2 patients), and ophthalmalgia (1 patient).. The addition of ripasudil was effective in lowering the IOP in patients with glaucoma poorly controlled with maximal medical therapy; moreover, the drug was well tolerated. In 48.5% of the patients in whom the predefined target IOP was achieved, this adjunctive therapy helped avoid glaucoma surgery at least in the short term.

Topics: Aged; Antihypertensive Agents; Drug Therapy, Combination; Enzyme Inhibitors; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Isoquinolines; Male; Maximum Tolerated Dose; Middle Aged; Ocular Hypertension; Ocular Hypotension; Prospective Studies; rho-Associated Kinases; Sulfonamides; Tonometry, Ocular

The aim of this study is to investigate the additive intraocular pressure (IOP)-lowering effects and safety of the selective Rho kinase inhibitor, 0.4% ripasudil, in patients with glaucoma not adequately controlled by other maximal tolerated medical therapies.. We retrospectively reviewed 92 glaucoma patients who received ripasudil as an additive glaucoma treatment. In spite of receiving prior maximal tolerated medical therapies, all patients had uncontrolled glaucoma before receiving ripasudil. IOP was recorded at all follow-up dates.. The study population consisted of 43 primary open-angle glaucoma (POAG), 28 normal-tension glaucoma (NTG), ten secondary glaucoma, seven exfoliation glaucoma, and four developmental glaucoma patients. After ripasudil administration, there was a significant decrease in the IOP. The mean pre-administration IOP and % IOP reduction at the last follow-up were 19.7 ± 4.9 mmHg and 6.5 ± 17.0% for POAG, 15.5 ± 2.0 mmHg and 2.3 ± 10.4% for NTG, 22.8 ± 8.3 mmHg and 19.1 ± 13.5% for secondary glaucoma, 22.5 ± 4.4 mmHg and 2.1 ± 14.5% for exfoliation glaucoma, and 20.2 ± 8.9 mmHg and 11.4 ± 23.1% for developmental glaucoma, respectively. Side effects led to ripasudil discontinuation in 13 patients, with five exhibiting an allergic reaction, six developing blepharitis, and two having a burning sensation.. Use of ripasudil as an adjunctive therapy resulted in lowering of the IOP. Ripasudil was well tolerated.. Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (26462689).

Topics: Adult; Aged; Antihypertensive Agents; Drug Monitoring; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Isoquinolines; Japan; Male; Maximum Tolerated Dose; Middle Aged; Retrospective Studies; rho-Associated Kinases; Sulfonamides; Tonometry, Ocular; Treatment Outcome