Rho Kinase (ROCK) Inhibitors in the Treatment of Glaucoma and Glaucoma Surgery: A Systematic Review of Early to Late Phase Clinical Trials

<b>Background/Objectives</b>: Primary open-angle glaucoma (POAG) is an anterior optic neuropathy that can lead to irreversible vision loss if untreated. Prostaglandin analogues are the first-line treatment, but new drug classes, such as rho kinase (ROCK) inhibitors, are being explored. T...

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Main Authors: Jit Kai Tan, Peng Tee Khaw, Christin Henein
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Pharmaceuticals
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Online Access:https://www.mdpi.com/1424-8247/18/4/523
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author Jit Kai Tan
Peng Tee Khaw
Christin Henein
author_facet Jit Kai Tan
Peng Tee Khaw
Christin Henein
author_sort Jit Kai Tan
collection DOAJ
description <b>Background/Objectives</b>: Primary open-angle glaucoma (POAG) is an anterior optic neuropathy that can lead to irreversible vision loss if untreated. Prostaglandin analogues are the first-line treatment, but new drug classes, such as rho kinase (ROCK) inhibitors, are being explored. This review evaluates the efficacy and safety of ROCK inhibitors in treating POAG based on completed trials, comparing results with available natural history data and identifying areas for further research. <b>Methods</b>: A systematic database search was conducted in Ovid MEDLINE and Ovid Embase on 5 April 2022 using the following keywords: ‘glaucoma’, ‘rho kinase inhibitor’, ‘rho-kinase inhibitor’, ‘rock inhibitor’, ‘ripasudil’, ‘netarsudil’, and ‘fasudil’. Abstracts were screened for relevant studies and results summarized in tables. <b>Results</b>: The analysis of trials conducted for ROCK inhibitors reveals that they are a safe and efficacious drug to treat POAG, demonstrating non-inferiority to existing medical treatments. Comparison of data to natural history studies was inconclusive due to the lack of natural history studies and their limitations. The results showed ROCK inhibitors to be effective when combined with existing medical treatments. However, questions remain regarding the optimal dosage, patient selection, and cost-effectiveness. Outcome measures for future trials should be expanded to include additional methods of monitoring disease progression as well as patient quality-of-life. <b>Conclusions</b>: ROCK inhibitors have emerged with a favorable safety profile, efficaciously attenuating intraocular pressure. To elucidate their long-term therapeutic value and safety comprehensively, further independent, large-scale, prospective randomized controlled trials are warranted. Such studies are pivotal to augment our understanding of this emergent medication class.
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spelling doaj-art-8e97dd2e589844d7a4823bb2aa12e6632025-08-20T02:18:20ZengMDPI AGPharmaceuticals1424-82472025-04-0118452310.3390/ph18040523Rho Kinase (ROCK) Inhibitors in the Treatment of Glaucoma and Glaucoma Surgery: A Systematic Review of Early to Late Phase Clinical TrialsJit Kai Tan0Peng Tee Khaw1Christin Henein2Guy’s Campus, King’s College London, London SE1 1UL, UKNational Institute for Health and Care Research Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital and University College London Institute of Ophthalmology, London EC1V 2PD, UKNational Institute for Health and Care Research Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital and University College London Institute of Ophthalmology, London EC1V 2PD, UK<b>Background/Objectives</b>: Primary open-angle glaucoma (POAG) is an anterior optic neuropathy that can lead to irreversible vision loss if untreated. Prostaglandin analogues are the first-line treatment, but new drug classes, such as rho kinase (ROCK) inhibitors, are being explored. This review evaluates the efficacy and safety of ROCK inhibitors in treating POAG based on completed trials, comparing results with available natural history data and identifying areas for further research. <b>Methods</b>: A systematic database search was conducted in Ovid MEDLINE and Ovid Embase on 5 April 2022 using the following keywords: ‘glaucoma’, ‘rho kinase inhibitor’, ‘rho-kinase inhibitor’, ‘rock inhibitor’, ‘ripasudil’, ‘netarsudil’, and ‘fasudil’. Abstracts were screened for relevant studies and results summarized in tables. <b>Results</b>: The analysis of trials conducted for ROCK inhibitors reveals that they are a safe and efficacious drug to treat POAG, demonstrating non-inferiority to existing medical treatments. Comparison of data to natural history studies was inconclusive due to the lack of natural history studies and their limitations. The results showed ROCK inhibitors to be effective when combined with existing medical treatments. However, questions remain regarding the optimal dosage, patient selection, and cost-effectiveness. Outcome measures for future trials should be expanded to include additional methods of monitoring disease progression as well as patient quality-of-life. <b>Conclusions</b>: ROCK inhibitors have emerged with a favorable safety profile, efficaciously attenuating intraocular pressure. To elucidate their long-term therapeutic value and safety comprehensively, further independent, large-scale, prospective randomized controlled trials are warranted. Such studies are pivotal to augment our understanding of this emergent medication class.https://www.mdpi.com/1424-8247/18/4/523glaucomaprimary open-angle glaucomaocular hypertensionrho kinase inhibitorsglaucoma filtration surgeryfibrosis
spellingShingle Jit Kai Tan
Peng Tee Khaw
Christin Henein
Rho Kinase (ROCK) Inhibitors in the Treatment of Glaucoma and Glaucoma Surgery: A Systematic Review of Early to Late Phase Clinical Trials
Pharmaceuticals
glaucoma
primary open-angle glaucoma
ocular hypertension
rho kinase inhibitors
glaucoma filtration surgery
fibrosis
title Rho Kinase (ROCK) Inhibitors in the Treatment of Glaucoma and Glaucoma Surgery: A Systematic Review of Early to Late Phase Clinical Trials
title_full Rho Kinase (ROCK) Inhibitors in the Treatment of Glaucoma and Glaucoma Surgery: A Systematic Review of Early to Late Phase Clinical Trials
title_fullStr Rho Kinase (ROCK) Inhibitors in the Treatment of Glaucoma and Glaucoma Surgery: A Systematic Review of Early to Late Phase Clinical Trials
title_full_unstemmed Rho Kinase (ROCK) Inhibitors in the Treatment of Glaucoma and Glaucoma Surgery: A Systematic Review of Early to Late Phase Clinical Trials
title_short Rho Kinase (ROCK) Inhibitors in the Treatment of Glaucoma and Glaucoma Surgery: A Systematic Review of Early to Late Phase Clinical Trials
title_sort rho kinase rock inhibitors in the treatment of glaucoma and glaucoma surgery a systematic review of early to late phase clinical trials
topic glaucoma
primary open-angle glaucoma
ocular hypertension
rho kinase inhibitors
glaucoma filtration surgery
fibrosis
url https://www.mdpi.com/1424-8247/18/4/523
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