Purpose: AKB-9778 is a small-molecule competitive inhibitor of vascular endothelial-protein tyrosine phosphatase (VE-PTP) that promotes Tie2 activation and reduces vascular leakage and neovascularization in mouse models. The purpose of this study was to test the safety, tolerability, pharmacokinetics, and biological activity of AKB-9778 in patients with diabetic macular edema (DME).
Design: Open-label, dose-escalation clinical trial.
Participants: Four dose cohorts of 6 patients with DME self-administered subcutaneous injections of 5 mg, 15 mg, 22.5 mg, or 30 mg AKB-9778 twice daily for 4 weeks.
Methods: Patients were seen weekly during a 4-week treatment period for safety assessments, best-corrected visual acuity (BCVA) assessment by Early Treatment Diabetic Retinopathy Study protocol, and measurement of central subfield thickness (CST) by spectral-domain optical coherence tomography. Additional safety assessments were performed at 6, 8, and 12 weeks.
Main Outcome Measures: Safety assessments, change from baseline BCVA, and change from baseline CST.
Results: All doses were well tolerated. A modest, transient reduction in blood pressure and adverse events consistent with vasodilatory activity of AKB-9778 emerged at doses of 22.5 mg or more twice daily. At the week 4 primary end point, BCVA improved 5 letters or more from baseline in 13 of the 18 patients receiving 15 mg or more twice daily; 1 patient improved by 10 to 15 letters, and 2 patients improved by more than 15 letters. Among 18 patients receiving 15 mg or more twice daily, CST decreased by more than 100 μm in 5 patients and by 50 to 100 μm in 2 patients. There was a significant correlation between reduction in CST and improvement in BCVA.
Conclusions: No safety concerns were identified after systemic administration of AKB-9778 for 4 weeks in patients with DME, and doses of 15 mg or more twice daily reduced macular edema and improved vision in some patients. This is a preliminary demonstration of clinical safety and efficacy of a VE-PTP inhibitor and Tie2 activator.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ophtha.2014.09.023 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Safety and Efficacy of Long-term Use of Infliximab in Severe Juvenile Dermatomyositis - 12 Years of Follow-up.
Acta Dermatovenerol Croat
November 2024
Prof. Marija Jelušić, MD, PhD, Department of Paediatrics, University of Zagreb, School of Medicine, Division of Clinical Immunology, Rheumatology and Allergology, Centre of Reference for Paediatric and Adolescent Rheumatology of Ministry of Health of the Republic Croatia, University Hospital Centre Zagreb, Kispaticeva 12, 10 000 Zagreb, Croatia;
Juvenile dermatomyositis with emphasized vasculopathy is rare, but the most severe form of the disease, with a poor prognosis with relapsing and chronic course or, in some cases, lethal outcome. We present a case of a 19-year-old Caucasian female, who developed severe acute juvenile dermatomyositis with emphasized multisystem vasculopathy, including retinal vasculopathy and maculopathy (cotton-wool spots, retinal hemorrhages, macular edema) at the age of 8. Due to no response to standard treatment protocols and rapid worsening of clinical symptoms and laboratory findings, a TNF inhibitor (infliximab) was introduced after the third week of treatment resulting in complete normalisation of muscle enzyme levels and complete resolution of eye changes within the next 2 weeks with a gradual general recovery.
View Article and Find Full Text PDFPurpose: The purpose of this study is to evaluate the impact of foveal bulge presence on visual acuity (VA) in patients with diabetic macular edema (DME) and retinal vein occlusion (RVO).
Methods: Spectral-domain optical coherence tomography (SD-OCT) scans were conducted on 22 DME patients and 20 RVO patients. Ordinary least squares (OLS) regression was employed to analyze the association between VA and the presence of the foveal bulge, as well as factors such as sex, age, central foveal thickness, various line scans of the fovea, and the external limiting membrane (ELM).
Visually significant ocular decompression retinopathy following laser peripheral iridotomy in a patient with primary acute angle-closure glaucoma.
Am J Ophthalmol Case Rep
December 2024
Department of Ophthalmology, Ross Eye Institute, University at Buffalo, 1176 Main Street, Buffalo, NY, 14209, United States.
Purpose: We report a single case of ocular decompression retinopathy (ODR) following neodymium-doped yttrium aluminum garnet laser peripheral iridotomy (Nd:YAG LPI) for primary acute angle-closure glaucoma associated with delayed visual recovery secondary to optic nerve head edema and macular thickening.
Observations: A 56-year-old female patient presented to the emergency department with primary acute angle-closure glaucoma. After topical and IV therapy did not improve intraocular pressure (IOP), an Nd:YAG LPI was performed.
Anterior Segment Optical Coherence Tomography Evaluation of a Dexamethasone Intravitreal Implant in the Crystalline Lens: A Case Report.
Int Med Case Rep J
January 2025
Department of Ophthalmology, Centro Hospitalar Universitário de São João, Porto, Portugal.
Purpose: Ozurdex is a dexamethasone intravitreal implant approved for the treatment of macular edema secondary to branch or central retinal vein occlusion, non-infectious uveitis affecting the posterior segment of the eye, and diabetic macular edema.
Patients And Methods: We report a case of an accidental injection of the implant into the crystalline lens, successfully managed by surgery afterwards. The case description is supported by Anterior Segment Optical Coherence Tomography (AS-OCT) images.
Purpose: To investigate the influence of systemic and serum measures and hypoglycemic medications on the initial presentation and ongoing development of diabetic retinopathy (DR) and diabetic macular edema (DME).
Design: Using Veterans Affairs electronic health records, we identified patients with a diabetes mellitus diagnosis and at least one eye examination between 1997 and 2010. After adjusting for sociodemographic factors, we used multivariable Cox regression models to evaluate the association of hemoglobin A1c (HbA1c) levels, blood pressure, albuminuria, blood urea nitrogen (BUN), and prescribed medications with the subsequent diagnosis of 1) any diabetic eye disease (defined for this analysis as DR and/or DME, 2) diabetic retinopathy, and 3) diabetic macular edema.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!