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05.01.2021 | Glaukom | Leitthema

Rho-Kinase-Hemmer als neue lokale Therapieoption beim primären Offenwinkelglaukom

verfasst von: Prof. Dr. C. Erb, K. Konieczka

Erschienen in: Die Ophthalmologie | Ausgabe 5/2021

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Zusammenfassung

Hintergrund

Im Jahr 2014 in Japan und 2017 in den USA wurden die Rho-Kinase-Hemmer als neue antiglaukomatöse Substanzgruppe zugelassen und sollen nun auch in Europa eingeführt werden.

Fragestellung

Aus diesem aktuellen Anlass soll der gegenwärtige Wissensstand zu den Rho-Kinase-Hemmern vorgestellt werden.

Methoden

In intensiver Recherche in PubMed wurde die relevante experimentelle und klinische Literatur zu den Rho-Kinase-Hemmern Ripasudil und Netarsudil sowie der Kombination aus Netarsudil und Latanoprost herausgesucht und für diese Übersicht zusammengestellt.

Ergebnisse

Die augeninnendrucksenkende Wirksamkeit von Ripasudil und Netarsudil liegt im Bereich des Betablockers Timolol und dem Prostaglandinanalogon Latanoprost. In der fixen Kombination Netarsudil/Latanoprost ist die Augeninnendrucksenkung stärker als die der Einzelkomponenten und erreicht in 32 % einen Zieldruckbereich von unter 15 mm Hg. Die konjunktivale Hyperämie mit 53–65 % ist die häufigste lokale Nebenwirkung. Systemische Nebenwirkungen sind sehr selten, und Kontraindikationen liegen bisher nicht vor.

Schlussfolgerungen

Rho-Kinase-Hemmer sind eine interessante Neueinführung für die Glaukomtherapie, da jede neue drucksenkende Therapie eine zusätzliche Chance darstellt, das individuell festgelegte Zieldruckniveau bei einem Glaukompatienten mit einer lokalen Therapie zu erreichen. Allerdings sind viele der mit den Rho-Kinase-Hemmern assoziierten pleiotropen Effekte bisher nur experimentell gefunden worden und bedürfen in Zukunft klinischer Bestätigung.

Wey S, Amanullah S, Spaeth GL et al (2019) Is primary open-angle glaucoma an ocular manifestation of systemic disease? Graefes Arch Clin Exp Ophthalmol 257:665–673PubMedCrossRef

Gupta N, Ang LC, Noël de Tilly L et al (2006) Human glaucoma and neural degeneration in intracranial optic nerve, lateral geniculate nucleus, and visual cortex. Br J Ophthalmol 90:674–678PubMedPubMedCentralCrossRef

Michelson G, Wärntges S, Engelhorn T et al (2012) Integrität/Demyelinisierung der Radiatio optica, Morphologie der Papille und Kontrastsensitivität bei Glaukompatienten. Klin Monatsbl Augenheilkd 229:143–148PubMedCrossRef

Nuzzi R, Dallorto L, Rolle T (2018) Changes of visual pathway and brain connectivity in glaucoma: a systematic review. Front Neurosci 12:363. https://doi.org/10.3389/fnins.2018.00363CrossRefPubMedPubMedCentral

Maier PC et al (2005) Treatment of ocular hypertension and open angle glaucoma: meta-analysis of randomised controlled trials. BMJ 331(7509):134PubMedPubMedCentralCrossRef

Flammer J, Orgül S, Costa VP, Orzalesi N, Krieglstein GK, Serra LM, Renard JP, Stefánsson E (2002) The impact of ocular blood flow in glaucoma. Prog Retin Eye Res 21(4):359–393. https://doi.org/10.1016/s1350-9462(02)00008-3 (PMID: 12150988)CrossRefPubMed

Leske MC, Heijl A, Hyman L, Bengtsson B, Dong L, Yang Z, Yang (2007) Predictors of long-term progression in the early manifest glaucoma trial. Ophthalmology 114(11):1965–1972. https://doi.org/10.1016/j.ophtha.2007.03.016 (EMGT Group)CrossRef

Erb C (2013) Pleiotrope Effekte in der lokalen medikamentösen Glaukomtherapie. Klin Monbl Augenheilkd 230(2):141–145. https://doi.org/10.1055/s-0032-1328164 (PMID: 23430678)CrossRefPubMed

CRSTEurope (2018) Rho-kinase inhibitor accepted for regulatory review in Europe. Cataract and Refractive Surgery Today, Bd. 11/12, S 12

10.

Coca-Prados M, Escribano J (2007) New perspectives in aqueous humor secretion and in glaucoma: the ciliary body as a multifunctional neuroendocrine gland. Prog Retin Eye Res 26(3):239–262. https://doi.org/10.1016/j.preteyeres.2007.01.002CrossRefPubMed

11.

Carreon T, van der Merwe E, Fellman RL, Johnstone M, Bhattacharya SK (2017) Aqueous outflow—A continuum from trabecular meshwork to episcleral veins. Prog Retin Eye Res 57:108–133PubMedCrossRef

12.

Costagliola C, dell’Omo R, Agnifili L, Bartollino S, Fea AM, Uva MG, Zeppa L, Mastropasqua L (2020) How many aqueous humor outflow pathways are there? Surv Ophthalmol 65(2):144–170. https://doi.org/10.1016/j.survophthal.2019.10.002 (PMID: 31622628)CrossRefPubMed

13.

Jünemann A, Hohberger B, Rech J et al (2018) Agonistic autoantibodies to the β2-Adrenergic receptor involved in the pathogenesis of open-angle glaucoma. Front Immunol 9:145. https://doi.org/10.3389/fimmu.2018.00145CrossRefPubMedPubMedCentral

14.

Hohberger B, Kunze R, Wallukat G et al (2019) Autoantibodies activating the β2-adrenergic receptor characterize patients with primary and secondary glaucoma. Front Immunol 10:2112. https://doi.org/10.3389/fimmu.2019.02112CrossRefPubMedPubMedCentral

15.

Larsson L, Rettig ES, Brubaker RF (1995) Aqueous flow in open-angle glaucoma. Arch Ophthalmol 113:283–286PubMedCrossRef

16.

Tripathi RC, Li J, Chan WF et al (1994) Aqueous humor in glaucomatous eyes contains an increased level of TGF-beta 2. Exp Eye Res 59:723–727PubMedCrossRef

17.

Gugleta K (2018) Significance of endothelin‑1 in glaucoma—A short overview. Klin Monbl Augenheilkd 235(2):140–145PubMed

18.

Fuchshofer R, Birke M, Welge-Lüssen U et al (2005) Transforming growth factor-beta 2 modulated extracellular matrix component expression in cultured human optic nerve head astrocytes. Invest Ophthalmol Vis Sci 46:568–578PubMedCrossRef

19.

Gottanka J, Chan D, Eichhorn M et al (2004) Effects of TGF-β2 in perfused human eyes. Invest Ophthalmol Vis Sci 45:153–158PubMedCrossRef

20.

Fuchshofer R (2011) Pathogenic role of transforming growth factor-β2 in glaucomatous damage to the optic nerve head. Exp Eye Res 93:165–169PubMedCrossRef

21.

O’Reilly S, Pollock N, Currie L et al (2011) Inducers of cross-linked actin networks in trabecular meshwork cells. Invest Ophthalmol Vis Sci 52:7316–7324PubMedCrossRef

22.

Yao K, Tan J, Gu WZ et al (2007) Reactive oxygen species mediates the apoptosis induced by transforming growth factor beta(2) in human lens epithelial cells. Biochem Biophys Res Commun 354:278–283PubMedCrossRef

23.

Zhong Y, Leung CK, Pang CP (2007) Glial cells and glaucomatous neuropathy. Chin Med J 120:326–335PubMedCrossRef

24.

Hammond TR, Marsh SE, Stevens B (2019) Immune signaling in neurodegeneration. Immunity 50:955–974PubMedPubMedCentralCrossRef

25.

D’Orléans-Juste P, Akide Ndunge OB, Desbiens L, Tanowitz HB, Desruisseaux MS (2019) Endothelins in inflammatory neurological diseases. Pharmacol Ther 194:145–160PubMedCrossRef

26.

Li S, Zhang A, Cao W, Sun X (2016) Elevated plasma endothelin‑1 levels in normal tension glaucoma and primary open-angle glaucoma: a meta-analysis. J Ophthalmol 2016:2678017PubMedPubMedCentralCrossRef

27.

Amin E, Dubey BN, Zhang SC, Gremer L, Dvorsky R, Moll JM, Taha MS, Nagel-Steger L, Piekorz RP, Somlyo AV, Ahmadian MR (2013) Rho-kinase: regulation, (dys)function, and inhibition. Biol Chem 394(11):1399–1410PubMedPubMedCentralCrossRef

28.

Rikitake Y, Liao JK (2005) Rho GTPases, statins, and nitric oxide. Circ Res 97(12):1232–1235PubMedPubMedCentralCrossRef

29.

Zhou Q, Liao JK (2009) Rho kinase: an important mediator of atherosclerosis and vascular disease. Curr Pharm Des 15(27):3108–3115PubMedPubMedCentralCrossRef

30.

Møller LLV, Klip A, Sylow L (2019) Rho GTPases-emerging regulators of glucose homeostasis and metabolic health. Cells 8(5):E434. https://doi.org/10.3390/cells8050434CrossRefPubMed

31.

Furukawa N, Ongusaha P, Jahng WJ, Araki K, Choi CS, Kim HJ, Lee YH, Kaibuchi K, Kahn BB, Masuzaki H et al (2005) Role of Rho-kinase in regulation of insulin action and glucose homeostasis. Cell Metab 2:119–129PubMedCrossRef

32.

Amin F, Ahmed A, Feroz A, Khaki PSS, Khan MS, Tabrez S, Zaidi SK, Abdulaal WH, Shamsi A, Khan W, Bano B (2019) An update on the association of protein kinases with cardiovascular diseases. Curr Pharm Des 25(2):174–183PubMedCrossRef

33.

Loirand G, Pacaud P (2014) Involvement of Rho GTPases and their regulators in the pathogenesis of hypertension. Small GTPases 5(4):1–10PubMedCrossRef

34.

Lai AY, McLaurin J (2018) Rho-associated protein kinases as therapeutic targets for both vascular and parenchymal pathologies in Alzheimer’s disease. J Neurochem 144(5):659–668PubMedCrossRef

35.

Labandeira-Garcia JL, Rodríguez-Perez AI, Villar-Cheda B, Borrajo A, Dominguez-Meijide A, Guerra MJ (2015) Rho kinase and dopaminergic degeneration: a promising therapeutic target for Parkinson’s disease. Neuroscientist 21:616–629PubMedCrossRef

36.

Nakazawa T (2016) Ocular blood flow and influencing factors for glaucoma. Asia Pac J Ophthalmol (Phila) 5(1):38–44CrossRef

37.

Gauthier AC, Liu J (2016) Neurodegeneration and neuroprotection in glaucoma. Yale J Biol Med 89(1):73–79 (eCollection 2016)PubMedPubMedCentral

38.

Benoist d’Azy C, Pereira B, Chiambaretta F, Dutheil F (2016) Oxidative and anti-oxidative stress markers in chronic glaucoma: a systematic review and meta-analysis. PLoS ONE 11(12):e166915. https://doi.org/10.1371/journal.pone.0166915 (eCollection 2016)CrossRefPubMedPubMedCentral

39.

Khawaja AP, Cooke Bailey JN, Kang JH et al (2016) Assessing the association of mitochondrial genetic variation with primary open-angle glaucoma using gene-set analyses. Invest Ophthalmol Vis Sci 57:5046–5052PubMedPubMedCentralCrossRef

40.

Abu-Amero KK, Kondkar AA, Chalam KV (2016) Mitochondrial aberrations and ophthalmic diseases. J Transl Sci 3:1–11CrossRef

41.

Knock GA, Ward JP (2011) Redox regulation of protein kinases as a modulator of vascular function. Antioxid Redox Signal 15(6):1531–1547PubMedCrossRef

42.

Torrejon KY, Papke EL, Halman JR, Bergkvist M, Danias J, Sharfstein ST, Xie Y (2016) TGFβ2-induced outflow alterations in a bioengineered trabecular meshwork are offset by a rho-associated kinase inhibitor. Sci Rep 7(6):38319. https://doi.org/10.1038/srep38319CrossRef

43.

Houde M, Desbiens L, D’Orléans-Juste P (2016) Endothelin-1: biosynthesis, signaling and vasoreactivity. Adv Pharmacol 77:143–175. https://doi.org/10.1016/bs.apha.2016.05.002CrossRefPubMed

44.

Wiederholt M, Thieme H, Stumpff F (2000) The regulation of trabecular meshwork and ciliary muscle contractility. Prog Retin Eye Res 19:271–295PubMedCrossRef

45.

Tamm ER, Braunger BM, Fuchshofer R (2015) Intraocular pressure and the mechanisms involved in resistance of the aqueous humor flow in the trabecular meshwork outflow pathways. Prog Mol Biol Transl Sci 134:301–314PubMedCrossRef

46.

Fuchshofer R, Tamm ER (2012) The role of TGF‑β in the pathogenesis of primary open-angle glaucoma. Cell Tissue Res 347:279–290PubMedCrossRef

47.

Sacca SC, Pascotto A, Camicione P, Capris P, Izzotti A (2005) Oxidative DNA damage in the human trabecular meshwork: clinical correlation in patients with primary open-angle glaucoma. Arch Ophthalmol 123(4):458–463PubMedCrossRef

48.

Rao PV, Deng PF, Kumar J, Epstein DL (2001) Modulation of aqueous humor outflow facility by the Rho kinase-specific inhibitor Y‑27632. Invest Ophthalmol Vis Sci 42(5):1029–1037PubMed

49.

Pattabiraman PP, Rao PV (2010) Mechanistic basis of Rho GTPase-induced extracellular matrix synthesis in trabecular meshwork cells. Am J Physiol Cell Physiol 298(3):C749–63PubMedCrossRef

50.

Babizhayev MA, Brodskaya MW (1989) Fibronectin detection in drainage outflow system of human eyes in ageing and progression of open-angle glaucoma. Mech Ageing Dev 47:145–157PubMedCrossRef

51.

Lutjen-Drecoll E, Futa R, Rohen JW (1981) Ultrahistochemical studies on tangential sections of the trabecular meshwork in normal and glaucomatous eyes. Invest Ophthalmol Vis Sci 21:563–573PubMed

52.

Rao PV, Pattabiraman PP, Kopczynski C (2017) Role of the rho GTPase/rho kinase signaling pathway in pathogenesis and treatment of glaucoma: bench to bedside research. Exp Eye Res 158:23–32PubMedCrossRef

53.

Thieme H, Nuskovski M, Nass JU, Pleyer U, Strauss O, Wiederholt M (2000) Mediation of calcium-independent contraction in trabecular meshwork through protein kinase C and rho‑A. Invest Ophthalmol Vis Sci 41(13):4240–4246 (PMID: 11095621)PubMed

54.

Pattabiraman PP, Maddala R, Rao PV (2014) Regulation of plasticity and fibrogenic activity of trabecular meshwork cells by Rho GTPase signaling. J Cell Physiol 229:927–942PubMedPubMedCentralCrossRef

55.

Fujimoto T, Inoue T, Ohira S, Awai-Kasaoka N, Kameda T, Inoue-Mochita M, Tanihara H (2017) Inhibition of rho kinase induces antioxidative molecules and suppresses reactive oxidative species in trabecular meshwork cells. J Ophthalmol 2017:7598140. https://doi.org/10.1155/2017/7598140 (PMID: 28804648; PMCID: PMC5540245)CrossRefPubMedPubMedCentral

56.

Rao PV, Deng PF, Kumar J, Epstein DL (2001) Modulation of aqueous humor outflow facility by the Rho kinase-specific inhibitor Y‑27632. Invest Ophthalmol Vis Sci 42(5):1029–1037PubMed

57.

Kaneko Y, Ohta M, Inoue T, Mizuno K, Isobe T, Tanabe S, Tanihara H (2016) Effects of K‑115 (Ripasudil), a novel ROCK inhibitor, on trabecular meshwork and Schlemm’s canal endothelial cells. Sci Rep 6:19640PubMedPubMedCentralCrossRef

58.

Kiel JW, Kopczynski CC (2015) Effect of AR-13324 on episcleral venous pressure in Dutch belted rabbits. J Ocul Pharmacol Ther 31(3):146–151. https://doi.org/10.1089/jop.2014.0146CrossRefPubMedPubMedCentral

59.

Kazemi A, McLaren JW, Kopczynski CC, Heah TG, Novack GD, Sit AJ (2018) The effects of Netarsudil ophthalmic solution on aqueous humor dynamics in a randomized study in humans. J Ocul Pharmacol Ther 34(5):380–386. https://doi.org/10.1089/jop.2017.0138CrossRefPubMedPubMedCentral

60.

Sturdivant JM, Royalty SM, Lin CW et al (2016) Discovery of the ROCK inhibitor netarsudil for the treatment of open-angle glaucoma. Bioorg Med Chem Lett 26(10):2475–2480. https://doi.org/10.1016/j.bmcl.2016.03.104CrossRefPubMed

61.

Wang RF, Williamson JE, Kopczynski C, Serle JB (2015) Effect of 0.04 % AR-13324, a ROCK, and norepinephrine transporter inhibitor, on aqueous humor dynamics in normotensive monkey eyes. J Glaucoma 24(1):51–54. https://doi.org/10.1097/IJG.0b013e3182952213CrossRefPubMed

62.

Li G, Mukherjee D, Navarro I et al (2016) Visualization of conventional outflow tissue responses to netarsudil in living mouse eyes. Eur J Pharmacol 787:20–31. https://doi.org/10.1016/j.ejphar.2016.04.002CrossRefPubMedPubMedCentral

63.

Chen S, Waxman S, Wang C, Atta S, Loewen R, Loewen NA (2020) Dose-dependent effects of netarsudil, a rho-kinase inhibitor, on the distal outflow tract. Graefes Arch Clin Exp Ophthalmol 258(6):1211–1216. https://doi.org/10.1007/s00417-020-04691-y (PMID: 32372330; PMCID: PMC7237522)CrossRefPubMedPubMedCentral

64.

Gauthier AC, Liu J (2016) Neurodegeneration and neuroprotection in glaucoma. Yale J Biol Med 89(1):73–79PubMedPubMedCentral

65.

Mélik Parsadaniantz S, Réaux-le Goazigo A, Sapienza A, Habas C, Baudouin C (2020) Glaucoma: a degenerative optic neuropathy related to neuroinflammation? Cells 9(3):535. https://doi.org/10.3390/cells9030535CrossRefPubMedCentral

66.

Koch JC, Tatenhorst L, Roser AE, Saal KA, Tönges L, Lingor P (2018) ROCK inhibition in models of neurodegeneration and its potential for clinical translation. Pharmacol Ther 189:1–21. https://doi.org/10.1016/j.pharmthera.2018.03.008CrossRefPubMed

67.

Kitaoka Y, Kitaoka Y, Kumai T et al (2004) Involvement of RhoA and possible neuroprotective effect of fasudil, a Rho kinase inhibitor, in NMDA-induced neurotoxicity in the rat retina. Brain Res 1018(1):111–118PubMedCrossRef

68.

Goldhagen B, Proia AD, Epstein DL, Rao PV (2012) Elevated levels of RhoA in the optic nerve head of human eyes with glaucoma. J Glaucoma 21(8):530–538. https://doi.org/10.1097/IJG.0b013e318241b83cCrossRefPubMed

69.

Yamamoto K, Maruyama K, Himori N et al (2014) The novel Rho kinase (ROCK) inhibitor K‑115: a new candidate drug for neuroprotective treatment in glaucoma. Invest Ophthalmol Vis Sci 55(11):7126–7136. https://doi.org/10.1167/iovs.13-13842CrossRefPubMed

70.

Shaw PX, Sang A, Wang Y et al (2017) Topical administration of a Rock/Net inhibitor promotes retinal ganglion cell survival and axon regeneration after optic nerve injury. Exp Eye Res 158:33–42. https://doi.org/10.1016/j.exer.2016.07.006CrossRefPubMed

71.

Fujita Y, Yamashita T (2014) Axon growth inhibition by RhoA/ROCK in the central nervous system. Front Neurosci 8:338. https://doi.org/10.3389/fnins.2014.00338CrossRefPubMedPubMedCentral

72.

Ellezam B, Dubreuil C, Winton M et al (2002) Inactivation of intracellular Rho to stimulate axon growth and regeneration. Prog Brain Res 137:371–380. https://doi.org/10.1016/s0079-6123(02)37028-6CrossRefPubMed

73.

Shaw PX, Sang A, Wang Y et al (2017) Topical administration of a rock/net inhibitor promotes retinal ganglion cell survival and axon regeneration after optic nerve injury. Exp Eye Res 158:33–42. https://doi.org/10.1016/j.exer.2016.07.006CrossRefPubMed

74.

Ichikawa M, Yoshida J, Saito K, Sagawa H, Tokita Y, Watanabe M (2008) Differential effects of two ROCK inhibitors, fasudil and Y‑27632, on optic nerve regeneration in adult cats. Brain Res 1201:23–33. https://doi.org/10.1016/j.brainres.2008.01.063CrossRefPubMed

75.

Townes-Anderson E, Wang J, Halász É et al (2017) Fasudil, a clinically used ROCK inhibitor, stabilizes Rod photoreceptor synapses after retinal detachment. Transl Vis Sci Technol 6(3):22. https://doi.org/10.1167/tvst.6.3.22CrossRefPubMedPubMedCentral

76.

Grieshaber MC, Mozaffarieh M, Flammer J (2007) What is the link between vascular dysregulation and glaucoma? Surv Ophthalmol 52(Suppl 2):S144–S154. https://doi.org/10.1016/j.survophthal.2007.08.010CrossRefPubMed

77.

Strassheim D, Gerasimovskaya E, Irwin D, Dempsey EC, Stenmark K, Karoor V (2019) RhoGTPase in vascular disease. Cells 8(6):551. https://doi.org/10.3390/cells8060551CrossRefPubMedCentral

78.

Hein TW, Rosa RH Jr, Yuan Z, Roberts E, Kuo L (2010) Divergent roles of nitric oxide and rho kinase in vasomotor regulation of human retinal arterioles. Invest Ophthalmol Vis Sci 51(3):1583–1590. https://doi.org/10.1167/iovs.09-4391 (PMID: 19850828; PMCID: PMC2868420)CrossRefPubMedPubMedCentral

79.

Tokushige H, Waki M, Takayama Y, Tanihara H (2011) Effects of Y‑39983, a selective Rho-associated protein kinase inhibitor, on blood flow in optic nerve head in rabbits and axonal regeneration of retinal ganglion cells in rats. Curr Eye Res 36(10):964–970. https://doi.org/10.3109/02713683.2011.599106CrossRefPubMed

80.

Wada Y, Higashide T, Nagata A, Sugiyama K (2019) Effects of ripasudil, a rho kinase inhibitor, on blood flow in the optic nerve head of normal rats. Graefes Arch Clin Exp Ophthalmol 257(2):303–311PubMedCrossRef

81.

Ohta Y, Takaseki S, Yoshitomi T (2017) Effects of ripasudil hydrochloride hydrate (K-115), a rho-kinase inhibitor, on ocular blood flow and ciliary artery smooth muscle contraction in rabbits. Jpn J Ophthalmol 61(5):423–432. https://doi.org/10.1007/s10384-017-0524-yCrossRefPubMed

82.

Potts LB, Ren Y, Lu G et al (2012) Constriction of retinal arterioles to endothelin-1: requisite role of rho kinase independent of protein kinase C and L‑type calcium channels. Invest Ophthalmol Vis Sci 53(6):2904–2912. https://doi.org/10.1167/iovs.12-9542CrossRefPubMedPubMedCentral

83.

Chihara E, Dimitrova G, Chihara T (2018) Increase in the OCT angiographic peripapillary vessel density by ROCK inhibitor ripasudil instillation: a comparison with brimonidine. Graefes Arch Clin Exp Ophthalmol 256(7):1257–1264. https://doi.org/10.1007/s00417-018-3945-5 (PMID: 29520478; PMCID: PMC6006239)CrossRefPubMedPubMedCentral

84.

Hopkins AA, Murphy R, Irnaten M, Wallace DM, Quill B, O’Brien C (2020) The role of lamina cribrosa tissue stiffness and fibrosis as fundamental biomechanical drivers of pathological glaucomatous cupping. Am J Physiol Cell Physiol. https://doi.org/10.1152/ajpcell.00054.2020CrossRefPubMed

85.

Downs JC, Girkin CA (2017) Lamina cribrosa in glaucoma. Curr Opin Ophthalmol 28(2):113–119. https://doi.org/10.1097/ICU.0000000000000354CrossRefPubMedPubMedCentral

86.

Pitha I, Oglesby E, Chow A, Kimball E, Pease ME, Schaub J, Quigley H (2018) Rho-kinase inhibition reduces myofibroblast differentiation and proliferation of scleral fibroblasts induced by transforming growth factor β and experimental glaucoma. Transl Vis Sci Technol 7(6):6. https://doi.org/10.1167/tvst.7.6.6 (PMID: 30479877; PMCID: PMC6238981)CrossRefPubMedPubMedCentral

87.

Erb C, Gast U, Schremmer D (2008) German register for glaucoma patients with dry eye. I. Basic outcome with respect to dry eye. Graefes Arch Clin Exp Ophthalmol 246(11):1593–1601. https://doi.org/10.1007/s00417-008-0881-9 (PMID: 18648841)CrossRefPubMed

88.

Baudouin C, Pisella PJ, Fillacier K, Goldschild M, Becquet F, De Saint Jean M, Béchetoille A (1999) Ocular surface inflammatory changes induced by topical antiglaucoma drugs: human and animal studies. Ophthalmology 106(3):556–563. https://doi.org/10.1016/S0161-6420(99)90116-1 (PMID: 10080214)CrossRefPubMed

89.

Lan W, Petznick A, Heryati S, Rifada M, Tong L (2012) Nuclear factor-κB: central regulator in ocular surface inflammation and diseases. Ocul Surf 10(3):137–148. https://doi.org/10.1016/j.jtos.2012.04.001 (PMID: 22814642)CrossRefPubMed

90.

Baudouin C, Labbé A, Liang H, Pauly A, Brignole-Baudouin F (2010) Preservatives in eyedrops: the good, the bad and the ugly. Prog Retin Eye Res 29(4):312–334. https://doi.org/10.1016/j.preteyeres.2010.03.001 (PMID: 20302969)CrossRefPubMed

91.

Tiedemann D, Mouhammad ZA, Utheim TP, Dartt DA, Heegaard S, Petrovski G, Kolko M (2019) Conjunctival goblet cells, the overlooked cells in glaucoma treatment. J Glaucoma 28(4):325–333. https://doi.org/10.1097/IJG.0000000000001168 (PMID: 30585937)CrossRefPubMed

92.

Trelford CB, Denstedt JT, Armstrong JJ, Hutnik CML (2020) The pro-fibrotic behavior of human tenon’s capsule fibroblasts in medically treated glaucoma patients. Clin Ophthalmol 14:1391–1402. https://doi.org/10.2147/OPTH.S245915 (PMID: 32546947; PMCID: PMC7250314)CrossRefPubMedPubMedCentral

93.

Cordeiro MF (2003) Role of transforming growth factor beta in conjunctival scarring. Clin Sci (Lond) 104(2):181–187. https://doi.org/10.1042/CS20020150 (Erratum in: Clin Sci (Lond) 2003; 105(6):723. PMID: 12546640)CrossRef

94.

Kaštelan S, Tomić M, Metež Soldo K, Salopek-Rabatić J (2013) How ocular surface disease impacts the glaucoma treatment outcome. Biomed Res Int 2013:696328. https://doi.org/10.1155/2013/696328 (PMID: 24224176; PMCID: PMC3809958)CrossRefPubMedPubMedCentral

95.

Yamanaka O, Kitano-Izutani A, Tomoyose K, Reinach PS (2015) Pathobiology of wound healing after glaucoma filtration surgery. BMC Ophthalmol 15(Suppl 1):157. https://doi.org/10.1186/s12886-015-0134-8 (PMID: 26818010; PMCID: PMC4895697)CrossRefPubMedPubMedCentral

96.

Yamada H, Yoneda M, Inaguma S, Gosho M, Murasawa Y, Isogai Z, Zako M (2017) A rho-associated kinase inhibitor protects permeability in a cell culture model of ocular disease, and reduces aqueous flare in anterior uveitis. J Ocul Pharmacol Ther 33(3):176–185. https://doi.org/10.1089/jop.2016.0085 (PMID: 28157424)CrossRefPubMed

97.

Futakuchi A, Inoue T, Fujimoto T, Inoue-Mochita M, Kawai M, Tanihara H (2016) The effects of ripasudil (K-115), a rho kinase inhibitor, on activation of human conjunctival fibroblasts. Exp Eye Res 149:107–115. https://doi.org/10.1016/j.exer.2016.07.001 (PMID: 27394186)CrossRefPubMed

98.

Ibrahim DG, Ko JA, Iwata W, Okumichi H, Kiuchi Y (2019) An in vitro study of scarring formation mediated by human tenon fibroblasts: effect of Y‑27632, a rho kinase inhibitor. Cell Biochem Funct 37(2):113–124. https://doi.org/10.1002/cbf.3382 (PMID: 30773659; PMCID: PMC6646872)CrossRefPubMedPubMedCentral

99.

Van de Velde S, Van Bergen T, Vandewalle E, Kindt N, Castermans K, Moons L, Stalmans I (2015) Rho kinase inhibitor AMA0526 improves surgical outcome in a rabbit model of glaucoma filtration surgery. Prog Brain Res 220:283–297. https://doi.org/10.1016/bs.pbr.2015.04.014 (PMID: 26497796)CrossRefPubMed

100.

Tanna AP, Johnson M (2018) Rho kinase inhibitors as a novel treatment for glaucoma and ocular hypertension. Ophthalmology 125(11):1741–1756. https://doi.org/10.1016/j.ophtha.2018.04.040 (PMID: 30007591; PMCID: PMC6188806)CrossRefPubMedPubMedCentral

101.

Kusuhara S, Nakamura M (2020) Ripasudil hydrochloride hydrate in the treatment of glaucoma: safety, efficacy, and patient selection. Clin Ophthalmol 14(6):1229–1236. https://doi.org/10.2147/OPTH.S216907 (PMID: 32440089; PMCID: PMC7212985)CrossRefPubMedPubMedCentral

102.

Inoue K, Ishida K, Tomita G (2018) Effectiveness and safety of switching from prostaglandin analog monotherapy to prostaglandin/timolol fixed combination therapy or adding ripasudil. Jpn J Ophthalmol 62(4):508–516. https://doi.org/10.1007/s10384-018-0599-0 (PMID: 29797109)CrossRefPubMed

103.

Dasso L, Al-Khaled T, Sonty S, Aref AA (2018) Profile of netarsudil ophthalmic solution and its potential in the treatment of open-angle glaucoma: evidence to date. Clin Ophthalmol 12:1939–1944. https://doi.org/10.2147/OPTH.S154001 (PMID: 30323550; PMCID: PMC6177382)CrossRefPubMedPubMedCentral

104.

Produktinformation zu Rhopressa. https://rhopressa.com/hcp/assets/pdf/RHOPRESSA-Prescribing-Information.pdf. Zugegriffen: 27. Sept. 2020

105.

Mehran NA, Sinha S, Razeghinejad R (2020) New glaucoma medications: latanoprostene bunod, netarsudil, and fixed combination netarsudil-latanoprost. Eye (Lond) 34(1):72–88. https://doi.org/10.1038/s41433-019-0671-0 (PMID: 31695162; PMCID: PMC7002400)CrossRef

106.

Sturdivant JM, Royalty SM, Lin CW, Moore LA, Yingling JD, Laethem CL, Sherman B, Heintzelman GR, Kopczynski CC, deLong MA (2016) Discovery of the ROCK inhibitor netarsudil for the treatment of open-angle glaucoma. Bioorg Med Chem Lett 26(10):2475–2480. https://doi.org/10.1016/j.bmcl.2016.03.104 (PMID: 27072905)CrossRefPubMed

107.

Kahook MY, Serle JB, Mah FS, Kim T, Raizman MB, Heah T, Ramirez-Davis N, Kopczynski CC, Usner DW, Novack GD, ROCKET‑2 Study Group (2019) Long-term safety and ocular hypotensive efficacy evaluation of netarsudil ophthalmic solution: rho kinase elevated IOP treatment trial (ROCKET-2). Am J Ophthalmol 200:130–137. https://doi.org/10.1016/j.ajo.2019.01.003 (PMID: 30653957)CrossRefPubMed

108.

Hollander DA, Aldave AJ (2004) Drug-induced corneal complications. Curr Opin Ophthalmol 15(6):541–548. https://doi.org/10.1097/01.icu.0000143688.45232.15 (PMID: 15523201)CrossRefPubMed

109.

Erb C (2015) Funktionelle Störungen im zeitlichen Verlauf der Glaukomerkrankung. Ophthalmologe 112:402–409PubMedCrossRef

110.

Produktinformation zu Rocklatan. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/208259s000lbl.pdf. Zugegriffen: 20. Okt. 2020

111.

Asrani S, Bacharach J, Holland E, McKee H, Sheng H, Lewis RA, Kopczynski CC, Heah T (2020) Fixed-dose combination of netarsudil and latanoprost in ocular hypertension and open-angle glaucoma: pooled efficacy/safety analysis of phase 3 MERCURY‑1 and -2. Adv Ther 37(4):1620–1631. https://doi.org/10.1007/s12325-020-01277-2 (PMID: 32166538; PMCID: PMC7140751)CrossRefPubMedPubMedCentral

112.

Shahbaz SK, Sadeghi M, Koushki K et al (2019) Regulatory T cells: possible mediators for the anti-inflammatory action of statins. Pharmacol Res 149:104469. https://doi.org/10.1016/j.phrs.2019.104469CrossRefPubMed

113.

Cai A, Zhou Y, Li L (2015) Rho-GTPase and atherosclerosis: pleiotropic effects of statins. J Am Heart Assoc 4(7):e2113. https://doi.org/10.1161/JAHA.115.002113 (PMID: 26124206; PMCID: PMC4608090)CrossRefPubMedPubMedCentral

114.

Song J, Deng PF, Stinnett SS, Epstein DL, Rao PV (2005) Effects of cholesterol-lowering statins on the aqueous humor outflow pathway. Invest Ophthalmol Vis Sci 46(7):2424–2432. https://doi.org/10.1167/iovs.04-0776 (PMID: 15980231)CrossRefPubMed

115.

Villarreal G Jr., Chatterjee A, Oh SS et al (2014) Pharmacological regulation of SPARC by lovastatin in human trabecular meshwork cells. Invest Ophthalmol Vis Sci 55:1657–1665PubMedPubMedCentralCrossRef

116.

Nagaoka T, Takahashi A, Sato E et al (2006) Effect of systemic administration of imvastatin on retinal circulation. Arch Ophthalmol 124:665–670PubMedCrossRef

117.

Lin HC et al (2010) Comparison of comorbid conditions between open-angle glaucoma patients and a control cohort: a casecontrol study. Ophthalmology 117:2088–2095PubMedCrossRef

Titel: Rho-Kinase-Hemmer als neue lokale Therapieoption beim primären Offenwinkelglaukom
verfasst von: Prof. Dr. C. Erb
K. Konieczka
Publikationsdatum: 05.01.2021
Verlag: Springer Medizin
Schlagwörter: Glaukom
Statine
Timolol
Latanoprost
Erschienen in: Die Ophthalmologie / Ausgabe 5/2021
Print ISSN: 2731-720X
Elektronische ISSN: 2731-7218
DOI: https://doi.org/10.1007/s00347-020-01303-2

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Springer Medizin

Rho-Kinase-Hemmer als neue lokale Therapieoption beim primären Offenwinkelglaukom

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Ophthalmika in der Schwangerschaft

Operative Therapie und Keimnachweis bei endogener Endophthalmitis

Bakterielle endogene Endophthalmitis

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Springer Medizin

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