Intravitreal injection of a Rho-kinase inhibitor (fasudil) combined with bevacizumab versus bevacizumab monotherapy for diabetic macular oedema: a pilot randomised clinical trial

Click here to listen to the PodcastBackground/aimsTo compare the efficacy of combined intravitreal injection of bevacizumab and a Rho-kinase inhibitor, fasudil (intravitreal bevacizumab (IVB)/intravitreal fasudil (IVF)), with IVB alone for centre-involving diabetic macular oedema (DME).MethodsIn this prospective randomised clinical trial, 44 eyes with centre-involving DME were randomised into two groups. The combined group received three consecutive injections of IVB (1.25 mg) and IVF (50 µM/L) monthly, while the monotherapy group received only one IVB (1.25 mg) injection per month for 3 months. Changes in best-corrected visual acuity (BCVA) and central macular thickness (CMT) were compared between the two groups at months 3 and 6. The primary outcome measure was the mean change in BCVA at month 6.ResultsMean BCVA was significantly improved in both groups at month 3 (P<0.001), but it persisted up to month 6 only in the IVB/IVF group. Improvement of BCVA was greater in the IVB/IVF group at both time points (P=0.008, P<0.001). In the IVB/IVF and IVB groups, 54.5% versus 10% of the eyes gained≥15 ETDRS letters at month 6 (P=0.026). Between months 3 and 6, mean BCVA significantly decreased by 5±7 ETDRS letters in the IVB group (P=0.002), while no significant deterioration was observed in the IVB/IVF group. Corresponding with the BCVA changes, CMT was significantly reduced in both groups at month 3 (p=0.006, p<0.001) but this reduction sustained only in the IVB/IVF group up to month 6 (p<0.001).ConclusionAdjunctive intravitreal injection of a Rho-kinase inhibitor may enhance and prolong the therapeutic effects of anti-vascular endothelial growth factor drugs for centre- involving DME.

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Preventive and therapeutic effects of the selective Rho-kinase inhibitor fasudil on experimental autoimmune neuritis

Journal of the Neurological Sciences ◽

10.1016/j.jns.2011.03.031 ◽

2011 ◽

Vol 306 (1-2) ◽

pp. 115-120 ◽

Cited By ~ 12

Author(s):

Arnold Angelo M. Pineda ◽

Motozumi Minohara ◽

Nobutoshi Kawamura ◽

Takuya Matsushita ◽

Ryo Yamasaki ◽

...

Keyword(s):

Kinase Inhibitor ◽

Rho Kinase ◽

Therapeutic Effects ◽

Experimental Autoimmune Neuritis ◽

Rho Kinase Inhibitor ◽

Experimental Autoimmune

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Double-Blind, Placebo-Controlled Clinical Trial With a Rho-Kinase Inhibitor in Pulmonary Arterial Hypertension

Circulation Journal ◽

10.1253/circj.cj-13-0443 ◽

2013 ◽

Vol 77 (10) ◽

pp. 2619-2625 ◽

Cited By ~ 96

Author(s):

Yoshihiro Fukumoto ◽

Norikazu Yamada ◽

Hiromi Matsubara ◽

Minori Mizoguchi ◽

Kazuaki Uchino ◽

...

Keyword(s):

Clinical Trial ◽

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Kinase Inhibitor ◽

Rho Kinase ◽

Controlled Clinical Trial ◽

Double Blind ◽

Double Blind Placebo ◽

Rho Kinase Inhibitor ◽

Pulmonary Arterial

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Protective Effects of Intravitreal Injection of the Rho-Kinase Inhibitor Y-27632 in a Rodent Model of Nonarteritic Anterior Ischemic Optic Neuropathy (rAION)

Journal of Ophthalmology ◽

10.1155/2020/1485425 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Zuohuizi Yi ◽

Liao Chen ◽

Xiaoling Wang ◽

Changzheng Chen ◽

Yiqiao Xing

Keyword(s):

Intravitreal Injection ◽

Optic Neuropathy ◽

Visual Function ◽

Kinase Inhibitor ◽

Rho Kinase ◽

Rodent Model ◽

Anterior Ischemic Optic Neuropathy ◽

Ischemic Optic Neuropathy ◽

Neuroprotective Effects ◽

Rho Kinase Inhibitor

Purpose. We sought to explore the effects of intravitreal injection of the Rho-kinase inhibitor Y-27632 in a rodent model of nonarteritic anterior ischemic optic neuropathy (rAION). Methods. The rAION model was established by using laser-induced photoactivation of intravenously administered Rose Bengal in rats. The rats received intravitreal injections of Y-27632 or PBS 1, 3, and 6 days after rAION induction. Optical coherence tomography (OCT) was performed at 2 days and 4 weeks after induction. Visual evoked potential (VEP) was used to evaluate the visual function at 4 weeks. Brn3a immunofluorescence staining of surviving RGCs and apoptosis assays of RGCs were performed at 4 weeks. Results. Optic nerve head (ONH) width was significantly reduced in the Y-27632 group compared with that in the PBS group at 2 days after induction (p<0.05). At 4 weeks, the P1 amplitude of flash-VEP (FVEP) in the Y-27632 group was significantly higher than that of the PBS group (p<0.05). The RGC densities in the central and midperipheral retinas in the Y-27632 group were significantly higher than those in the PBS group (p<0.05). Furthermore, there was a significant decrease in apoptotic RGCs in the Y-27632 group than in the PBS group (p<0.05). Conclusions. Intravitreal injection of Y-27632 had neuroprotective effects on ONH edema, RGC survival, and visual function preservation in rAION.

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Evaluation of offset of conjunctival hyperemia induced by a Rho-kinase inhibitor; 0.4% Ripasudil ophthalmic solution clinical trial

Scientific Reports ◽

10.1038/s41598-019-40255-9 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 8

Author(s):

Emi Sakamoto ◽

Waka Ishida ◽

Tamaki Sumi ◽

Tatsuma Kishimoto ◽

Kentaro Tada ◽

...

Keyword(s):

Clinical Trial ◽

Kinase Inhibitor ◽

Rho Kinase ◽

Ophthalmic Solution ◽

Conjunctival Hyperemia ◽

Rho Kinase Inhibitor

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Intravitreal Injection of a Rho-Kinase Inhibitor (Fasudil) for Recent-Onset Nonarteritic Anterior Ischemic Optic Neuropathy

The Journal of Clinical Pharmacology ◽

10.1002/jcph.655 ◽

2015 ◽

Vol 56 (6) ◽

pp. 749-753 ◽

Cited By ~ 7

Author(s):

Nasrin Sanjari ◽

Mohammad Pakravan ◽

Ramin Nourinia ◽

Hamed Esfandiari ◽

Ali Hafezi-Moghadam ◽

...

Keyword(s):

Intravitreal Injection ◽

Optic Neuropathy ◽

Kinase Inhibitor ◽

Rho Kinase ◽

Anterior Ischemic Optic Neuropathy ◽

Ischemic Optic Neuropathy ◽

Recent Onset ◽

Rho Kinase Inhibitor

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Short-term vision gains at 12 weeks correlate with long-term vision gains at 2 years: results from the BEVORDEX randomised clinical trial of bevacizumab versus dexamethasone implants for diabetic macular oedema

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2017-310737 ◽

2017 ◽

Vol 102 (4) ◽

pp. 479-482 ◽

Cited By ~ 5

Author(s):

Hemal Mehta ◽

Samantha Fraser-Bell ◽

Vuong Nguyen ◽

Lyndell L Lim ◽

Mark C Gillies

Keyword(s):

Clinical Trial ◽

Macular Oedema ◽

Diabetic Macular Oedema ◽

Randomised Clinical Trial ◽

Macular Thickness ◽

Central Macular Thickness ◽

Short Term ◽

Treatment Allocation ◽

Visual Outcomes

AimTo determine whether early vision gains predict long-term visual outcomes in the BEVORDEX randomised clinical trial of bevacizumab or dexamethasone implants for diabetic macular oedema.MethodsPost hoc analysis of 68 study eyes (77%) that completed 2 years follow-up of the BEVORDEX multicentre randomised clinical trial set in Australia (ClinicalTrials.gov identifier: NCT01298076). Study eyes from both groups were combined and stratified by visual acuity (VA) change in the first 12 weeks in to three groups: (a) suboptimal gain: <5 letters gain (includes VA loss), (b) moderate gain: 5–9 letters gain, (c) pronounced gain: ≥10 letters gain. This was correlated with VA outcome at 104 weeks taking into account treatment allocation and baseline lens status.ResultsThe change in VA in the first 12 weeks was significantly correlated with VA change at 104 weeks (p<0.001). This was independent of treatment allocation (p=0.353) and lens status at baseline (p=0.593). The change in central macular thickness at 12 weeks did not correlate with VA gain at 104 weeks (p=0.847).ConclusionShort-term visual gain at 12 weeks was strongly correlated with long-term vision improvement independent of treatment allocation or baseline lens status. Early improvement in central macular thickness was not predictive of long-term visual outcomes.Trial registration numberNCT01298076, Post-results.

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Prospective randomised clinical trial of intravitreal bevacizumab versus triamcinolone in eyes with diabetic macular oedema undergoing cataract surgery: 6-month results

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2018-313437 ◽

2019 ◽

pp. bjophthalmol-2018-313437 ◽

Cited By ~ 3

Author(s):

Rathika Kandasamy ◽

Marios Constantinou ◽

Sophie L Rogers ◽

Sukhpal Singh Sandhu ◽

Sanjeewa Wickremasinghe ◽

...

Keyword(s):

Clinical Trial ◽

Cataract Surgery ◽

Macular Oedema ◽

Diabetic Macular Oedema ◽

Intravitreal Bevacizumab ◽

Randomised Clinical Trial ◽

Sustained Improvement ◽

Significant Difference ◽

To Receive ◽

Significant Cataract

AimTo report the 6-month results of a clinical trial that compared intravitreous bevacizumab (BVB) 1.25 mg versus triamcinolone acetonide (TA) 4 mg when administered as an adjunct during cataract surgery to patients with diabetic macular oedema (DMO).MethodsProspective, double-masked, single-centre (Royal Victorian Eye and Ear Hospital, Melbourne) clinical trial. Patients with visually significant cataract and centre-involving DMO (either current or prior) were randomised (1: 1) to receive either intravitreous BVB 1.25 mg or TA 4 mg at the time of cataract surgery and if required at review. Main outcome measures were changes in best-corrected visual acuity (BCVA) and central macular thickness (CMT) from baseline to the 6-month time point of this 12-month study.Results61 eyes of 58 patients were enrolled. At baseline, both groups were similar in terms of BCVA and CMT (p>0.2). At 6 months, there was no significant difference in vision between the groups, with mean letter gain of +21.4 (95% CI +14.5 to +28.4) in the TA group and +17.3 (95% CI +12.1 to +22.6) in the BVB group (p=0.35). The TA group had a significant sustained anatomical improvement at 6 months, with a reduction in CMT (−51.4 µm; 95% CI −98.2 to -4.7) compared with thickening in the BVB group (+15.6 µm; 95% CI −26.4 to +57.7, p=0.04).ConclusionsWhen given as an adjunct to cataract surgery, both TA and BVB improved visual outcomes at 6 months postoperatively. However, only TA resulted in sustained improvement in CMT, with the majority not requiring any further treatment postoperatively.

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