Potential Functional Restoration of Corneal Endothelial Cells in Fuchs Endothelial Corneal Dystrophy by ROCK Inhibitor (Ripasudil)

Schlötzer‐Schrehardt, Ursula; Zenkel, Matthias; Strunz, Maria; Gießl, Andreas; Schondorf, Hannah; Silva, Heather da; Schmidt, Gregory A.; Greiner, Mark A.; Okumura, Naoki; Koizumi, Noriko; Kinoshita, Shigeru; Tourtas, Theofilos; Kruse, Friedrich E.

doi:10.1016/j.ajo.2020.12.006

Cited by 57 publications

(51 citation statements)

References 61 publications

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“…While some investigations have shown that ripasudil causes a temporary morphologic change of corneal endothelial cells in humans and animals [27,28], this has not translated into an increased risk of developing corneal disorders in patients with glaucoma receiving ripasudil [24,29,30]. Furthermore, ROCK inhibitors, such as Y-27632 and ripasudil, are regarded as a having regenerative effect on diseased corneal endothelial cells [31,32]. Taking these points into consideration, the final results of this PMS study show that the clinical properties of ripasudil are different from those of In line with other clinical trials of ripasudil [24,29,30,33] and previous interim analyses of this PMS study [15,16], IOP was significantly reduced with ripasudil in this final analysis of the PMS study.…”

Section: Confidence Interval Hr Hazard Ratiomentioning

confidence: 99%

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

et al. 2022

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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-naı ¨ve 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. Results: 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 leastsquares 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, normaltension glaucoma, primary angle-closure glaucoma, and secondary glaucoma, and ocular hypertension. Conclusion: Ripasudil was safe and effective as an antiglaucoma medication with no new safety signals identified and significant reductions in

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Section: Confidence Interval Hr Hazard Ratiomentioning

confidence: 99%

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

et al. 2022

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“…Moreover, Davies [ 59 ] recently observed that netarsudil could be effective in achieving corneal clearance in different cases of endothelial dysfunction that may present in a daily cornea practice, such as iridocorneal endothelial syndrome, after an early PK graft failure and after a chronic PK graft failure. Likewise, this has recently been verified by Schlötzer-Schrehardt et al [ 60 ] in a large database with an ex vivo FECD tissue culture model, where a single dose of ripasudil induced a significant upregulation of genes and proteins related to cell cycle progression, adhesion, and migration of the cellular matrix, as well as increasing the endothelial pump and barrier function up to 72 hours after instillation without inducing adverse phenotypic changes.…”

Section: Rock Inhibitorsmentioning

confidence: 58%

New Horizons in the Treatment of Corneal Endothelial Dysfunction

Rocha‐de‐Lossada

Rachwani-Anil

Borroni

et al. 2021

Journal of Ophthalmology

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The treatment of corneal endothelial dysfunction has experienced a revolutionary change in the past decades with the emergence of endothelial keratoplasty techniques: descemet stripping automated endothelial keratoplasty (DSAEK) and descemet membrane endothelial keratoplasty (DMEK). Recently, new treatments such as cultivated endothelial cell therapy, Rho-kinase inhibitors (ROCK inhibitors), bioengineered grafts, and gene therapy have been described. These techniques represent new lines of treatment for endothelial dysfunction. Their advantages are to help address the shortage of quality endothelial tissue, decrease the complications associated with tissue rejection, and reduce the burden of postoperative care following transplantation. Although further randomized clinical trials are required to validate these findings and prove the long-term efficacy of the treatments, the positive outcomes in preliminary clinical studies are a stepping stone to a promising future. Our aim is to review the latest available alternatives and advancements to endothelial corneal transplant.

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“…4 Different mechanisms have been proposed to describe the mechanism of benefit of ripasudil with migration, proliferation, or both, being the driving forces of endothelial regeneration. 11 It was also shown that ripasudil induced upregulation of proteins important for endothelial pump and barrier function, indicating that the restored endothelial cells were functionally competent. 11 Given the Descemet bubble limits normal endothelial migration in our patient, it is likely that the improved endothelial pump function induced by ripasudil is the cause of clinical improvement (Figure 2).…”

Section: Discussionmentioning

confidence: 99%

Corneal endothelial wound healing after Descemet tear with a rho kinase inhibitor

Azhari

Patel

Vakharia

2022

JCRS Online Case Rep

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Introduction:To the authors’ knowledge, this is the first report of Descemet tear postcataract surgery that was successfully treated with ripasudil hydrochloride hydrate.Patient and Clinical Findings:An 85-year-old pseudophakic man presented with blurry vision and mild photophobia in the left eye. Slitlamp biomicroscopy showed moderate corneal edema and a central Descemet tear from cataract surgery 7 years earlier.Diagnosis, Intervention, and Outcomes:The patient was treated for 1 month with prednisolone acetate 1% and sodium chloride 5% hyperosmotic ophthalmic solution with no clinical improvement. He declined surgical intervention and opted for medical management with ripasudil 0.4% ophthalmic solution, a rho kinase inhibitor. He applied it topically 4 times daily for 3 months, with improvement of corneal edema and corrected distance visual acuity. After discontinuation of ripasudil, his edema and vision worsened and then improved again after retreatment, showing a strong clinical response. 2 years after starting ripasudil therapy, the patient had continued to use ripasudil 3 times daily and reported worsened vision at lower doses.Conclusions:The use of topical ripasudil may be a viable medical intervention for corneal edema due to Descemet tear instead of surgery, although chronic use may be required.

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Potential Functional Restoration of Corneal Endothelial Cells in Fuchs Endothelial Corneal Dystrophy by ROCK Inhibitor (Ripasudil)

Cited by 57 publications

References 61 publications

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

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

New Horizons in the Treatment of Corneal Endothelial Dysfunction

Corneal endothelial wound healing after Descemet tear with a rho kinase inhibitor

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