glanatec and Hyperemia

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

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

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

We investigated the effects of instillation of ripasudil hydrochloride hydrate (GLANATEC. Fourteen healthy participants (mean age: 30 years), who had no ophthalmic diseases other than refractive error, were enrolled in this study. A single dose of GLANATEC. The IOP in the left eye was significantly lower at both 30 (p < 0.05) and 120 (p < 0.01) min after instillation than at baseline, whereas that in the right eye was not significantly different from baseline at either of the measured post-instillation time points. In contrast, the pupillary response did not significantly differ between the three time points.. A single instillation of low concentration GLANATEC

Topics: Administration, Topical; Adult; Conjunctiva; Dark Adaptation; Female; Humans; Hyperemia; Intraocular Pressure; Isoquinolines; Male; Muscle, Smooth; Ophthalmic Solutions; Pupil; Reflex, Pupillary; rho-Associated Kinases; Sulfonamides

We investigated the detailed time course of conjunctival hyperemia induced by ripasudil 0.4%, a novel Rho-kinase inhibitor anti-glaucoma eye drop, in healthy subjects.. We recruited 51 healthy subjects and administered ripasudil 0.4% in their right eye. We evaluated conjunctival hyperemia using slit lamp photography and measured the intraocular pressure (IOP) using the Icare PRO Rebound Tonometer at baseline and after 5, 15, 30, 60, 90, and 120 min. The conjunctival hyperemia score was graded by three independent observers on a scale of 0 (none) to 3 (severe). Additionally, we analyzed the "percent coverage" of conjunctival hyperemia by using an automated hyperemia analysis software program; this program provides the pixel coverage of the conjunctival vessels in the region of interest. Dunnett and Steel multiple comparison tests were used, as appropriate, for the subsequent analyses.. The conjunctival hyperemia score and percent coverage increased rapidly after the instillation of ripasudil 0.4%, peaking at 15 min (score: 1.83 ± 0.29 [mean ± SD]) and 5 min (11.6% ± 4.7%), respectively, and then gradually decreasing until 120 min (0.45 ± 0.22 and 4.7% ± 1.8%, respectively), when they reached a level that was not significantly different from the baseline values. The IOP decreased significantly compared to the baseline at 30, 60, and 90 min, based on the Dunnett test.. Conjunctival hyperemia induced by ripasudil 0.4% peaks rapidly to moderate severity, but subsides relatively quickly.

Topics: Adult; Conjunctiva; Conjunctival Diseases; Female; Glaucoma; Healthy Volunteers; Humans; Hyperemia; Intraocular Pressure; Isoquinolines; Male; Middle Aged; Ophthalmic Solutions; rho-Associated Kinases; Severity of Illness Index; Sulfonamides; Young Adult