{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T22:16:06Z","timestamp":1780956966830,"version":"3.54.1"},"reference-count":28,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T00:00:00Z","timestamp":1756339200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Pseudophakic bullous keratopathy (PBK) is a vision-threatening corneal complication following cataract surgery, characterised by progressive endothelial cell loss, persistent corneal oedema, and painful epithelial bullae, leading to impaired vision. Corneal transplantation, either penetrating or endothelial keratoplasty, remains the primary treatment but faces challenges such as donor tissue shortages, graft rejection, and limited graft longevity. Recently, Rho-kinase (ROCK) inhibitors have emerged as promising pharmacological alternatives. These agents enhance corneal endothelial cell proliferation, migration, and adhesion, suppress apoptosis, and promote corneal deturgescence and wound healing. Several preclinical and clinical studies have demonstrated the efficacy of ROCK inhibitors in improving corneal clarity, endothelial function, and visual acuity in PBK. Their use has been associated with reductions in corneal oedema, improved endothelial cell density, and delayed or prevented the need for corneal transplantation. A systematic literature search of PubMed, Scopus, and Web of Science databases was conducted, restricted to peer-reviewed English-language articles, ensuring comprehensive coverage. ROCK inhibitors represent a novel pharmacological strategy for PBK prevention and management, potentially reducing dependency on donor grafts. Further research is needed to determine long-term safety, optimal dosing, and efficacy.<\/jats:p>","DOI":"10.3390\/jcm14176093","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T15:03:14Z","timestamp":1756393394000},"page":"6093","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["RhoKinase (ROCK) Inhibition as a Therapeutic Strategy for Pseudophakic Bullous Keratopathy: A Comprehensive Review"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0051-0003","authenticated-orcid":false,"given":"An\u0111ela","family":"Juki\u0107","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, University Hospital Dubrava, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josip","family":"Pavan","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Hospital Dubrava, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6566-501X","authenticated-orcid":false,"given":"Biljana","family":"\u0110apic Ivan\u010di\u0107","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital Centre Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miro","family":"Kalauz","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Hospital Centre Zagreb, 10000 Zagreb, Croatia"},{"name":"School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajka","family":"Kasalica \u017du\u017eul","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Hospital Dubrava, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomislav","family":"Juki\u0107","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Hospital Centre Zagreb, 10000 Zagreb, Croatia"},{"name":"School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1186\/s13256-025-05263-6","article-title":"Managing pseudophakic bullous keratopathy with a topical rho kinase inhibitor: A case series","volume":"19","author":"Erdinest","year":"2025","journal-title":"J. Med. Case Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"97","DOI":"10.2147\/DDDT.S435522","article-title":"The role of Rho kinase inhibitors in corneal diseases","volume":"18","author":"Futterknecht","year":"2024","journal-title":"Drug. Des. Devel. Ther."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Ghenciu, L.A., Andrei, D., Borza, C., Iacob, R., Stoicescu, E.R., Bolintineanu, S.L., Iacob, D., and Ha\u0163egan, O.A. (2025). Therapeutic Potential of Rho Kinase Inhibitors in Corneal Disease: A Systematic Review of Preclinical and Clinical Studies. Biomedicines, 13.","DOI":"10.3390\/biomedicines13071602"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1167\/iovs.15-18586","article-title":"Effect of the Rho-associated kinase inhibitor eye drop (ripasudil) on corneal endothelial wound healing","volume":"57","author":"Okumura","year":"2016","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1167\/iovs.13-12225","article-title":"Involvement of cyclin D and p27 in cell proliferation mediated by ROCK inhibitors Y-27632 and Y-39983 during corneal endothelium wound healing","volume":"55","author":"Okumura","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"6067","DOI":"10.1167\/iovs.15-17595","article-title":"Effect of the Rho Kinase Inhibitor Y-27632 on Corneal Endothelial Wound Healing","volume":"56","author":"Okumura","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Peh, G.S.L., Adnan, K., George, B.L., Ang, H.-P., Seah, X.-Y., Tan, D.T., and Mehta, J.S. (2015). The effects of Rho-associated kinase inhibitor Y-27632 on primary human corneal endothelial cells propagated using a dual media approach. Sci. Rep., 5.","DOI":"10.1038\/srep09167"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2493","DOI":"10.1167\/iovs.12-11320","article-title":"The ROCK inhibitor eye drop accelerates corneal endothelium wound healing","volume":"54","author":"Okumura","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1056\/NEJMoa1712770","article-title":"Injection of cultured cells with a ROCK inhibitor for bullous keratopathy","volume":"378","author":"Kinoshita","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1097\/ICO.0000000000003282","article-title":"Topical ripasudil for the treatment of segmental corneal edema: A case series","volume":"42","author":"Tseng","year":"2023","journal-title":"Cornea"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Gaudenzi, D., De Gregorio, C., Cutrupi, F., Branda, F., Coassin, M., and Di Zazzo, A. (Eur. J. Ophthalmol., 2025). Rock-Inhibitors eyedrops preventing cataract surgery induced corneal failure in Fuchs corneal dystrophy, Eur. J. Ophthalmol., epub ahead of print.","DOI":"10.1177\/11206721251351154"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1097\/ICO.0000000000003827","article-title":"Efficacy of the Rho-Kinase Inhibitor for Corneal Endothelial Protection in Fuchs Endothelial Corneal Dystrophy After Phacoemulsification","volume":"44","author":"Keeratidamkerngsakul","year":"2025","journal-title":"Cornea"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1167\/tvst.10.4.18","article-title":"The ROCK inhibitor ripasudil shows an endothelial protective effect in patients with low corneal endothelial cell density after cataract surgery","volume":"10","author":"Fujimoto","year":"2021","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1007\/s40123-024-00950-x","article-title":"The protective effect of Rho-associated kinase inhibitor eye drops (ripasudil) on corneal endothelial cells after cataract surgery: A prospective comparative study","volume":"13","author":"Alkharashi","year":"2024","journal-title":"Ophthalmol. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"101245","DOI":"10.1016\/j.ajoc.2021.101245","article-title":"Rho-associated kinase inhibitor eye drops in challenging cataract surgery","volume":"25","author":"Antonini","year":"2022","journal-title":"Am. J. Ophthalmol. Case Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/j.ophtha.2020.09.002","article-title":"Five-year follow-up of first-in-human corneal endothelial cell injection therapy for corneal endothelial failure","volume":"128","author":"Numa","year":"2021","journal-title":"Ophthalmology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1007\/s10384-024-01123-w","article-title":"Phase II and III studies of injection of cultured corneal endothelial cells in bullous keratopathy","volume":"68","author":"Ueno","year":"2024","journal-title":"Jpn. J. Ophthalmol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Holland, E.J., Yeu, E., Giegengack, M., Berdahl, J., Jordan, E.O., Quesada, R., Quesada, G., Kinoshita, S., Sotozono, C., and Toda, M. (Cornea, 2025). Escal\u00f3n: A Prospective Randomized Trial of Corneal Endothelial Cell Therapy in Subjects with Corneal Edema, Cornea, epub ahead of print.","DOI":"10.1097\/ICO.0000000000003844"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"101847","DOI":"10.1016\/j.xcrm.2024.101847","article-title":"A first-in-human clinical study of an allogenic iPSC-derived corneal endothelial cell substitute transplantation for bullous keratopathy","volume":"6","author":"Hirayama","year":"2025","journal-title":"Cell Rep. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"88","DOI":"10.4103\/tjo.TJO-D-23-00169","article-title":"Evaluating the efficacy of Rho kinase inhibitor eye drops in the management of corneal edema: A single-center retrospective cohort study","volume":"14","author":"Lavy","year":"2024","journal-title":"Taiwan J. Ophthalmol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Erdinest, N., Tabi, M., Shemesh, N., Corredores, J., Yahalom, C., Eshel, Y., Stern, B., Smadja, D., Gur, Z., and Lavy, I. (2025). Clinical Evaluation of Ripasudil for Corneal Edema: A Large-Scale Retrospective Cohort Study. J. Clin. Med., 14.","DOI":"10.3390\/jcm14155572"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1016\/j.jcrs.2018.04.044","article-title":"Prophylactic exposure of human corneal endothelial cells to Rho-associated kinase inhibitor reduced apoptosis rate after phacoemulsification: Ex vivo study","volume":"44","author":"Achiron","year":"2018","journal-title":"J. Cataract Refract. Surg."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Leong, E.Y.X., Ding, J., Wu, D., Lim, B.X.H., Ang, A., Wong, E., Morlet, N., Mehta, J.S., and Lim, C.H.L. (2025). A Comprehensive Review of the Role of Rho-Kinase Inhibitors in Corneal Diseases. Life, 15.","DOI":"10.3390\/life15081283"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Juki\u0107, A., Bakra\u010d, A.P., Ivan\u010di\u0107, B.\u0110., Kopi\u0107, A., Meter, A., \u017du\u017eul, R.K., Pavan, J., and Juki\u0107, T. (2025). Rho-Kinase Inhibitors in the Management of Fuchs Endothelial Corneal Dystrophy: A Review. Medicina, 61.","DOI":"10.3390\/medicina61050772"},{"key":"ref_25","first-page":"9","article-title":"Rho-kinase inhibitors: Role in corneal endothelial disorders","volume":"38","author":"Singh","year":"2023","journal-title":"Taylor Fr."},{"key":"ref_26","first-page":"1348","article-title":"Retreatment of ICE syndrome-related corneal edema with a ROCK inhibitor: A case report","volume":"40","author":"Davies","year":"2021","journal-title":"Cornea"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"6843","DOI":"10.1167\/iovs.16-20123","article-title":"Activation of the Rho\/Rho Kinase Signaling Pathway Is Involved in Cell Death of Corneal Endothelium","volume":"57","author":"Okumura","year":"2016","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_28","first-page":"5","article-title":"Rho kinase inhibitors for corneal diseases: Review of the literature and perspectives","volume":"12","author":"Chaurasia","year":"2023","journal-title":"Asia Pac. J. Ophthalmol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/17\/6093\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:34:38Z","timestamp":1760034878000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/17\/6093"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,28]]},"references-count":28,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["jcm14176093"],"URL":"https:\/\/doi.org\/10.3390\/jcm14176093","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,28]]}}}