| Topical mecamylamine for diabetic macular edema. | |
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MedLine Citation:
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PMID: 20189159 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: Stimulation of nicotinic acetylcholine (nACh) receptors on vascular endothelial cells promotes angiogenesis and vascular permeability in animal models. The safety and bioactivity of topical mecamylamine, an antagonist of nACh receptors, was tested in patients with diabetic macular edema. DESIGN: A multicenter phase I/II clinical trial. METHODS: Twenty-three patients with chronic diabetic macular edema received 1% mecamylamine topically twice daily for 12 weeks, the primary end point. Patients underwent safety assessments, measurement of best-corrected visual acuity (BCVA), and measurement of foveal thickness using optical coherence tomography at baseline, 1, 4, 8, 12, and 16 weeks. RESULTS: Mecamylamine drops were well tolerated and there were no drug-related safety problems. Mean improvement in BCVA at 1, 4, 8, 12, and 16 weeks was 2.8, 1.9, 2.4, 0.8, and 3.1 letters, respectively. There was little change in mean excess foveal thickness. There was substantial heterogeneity in response, because 8 patients showed convincing improvement in BCVA, foveal thickness, or both, 9 patients showed equivocal or no substantial changes, and 4 patients showed worsening. Five patients showed a substantial improvement in BCVA, foveal thickness, or both between their last visit while receiving mecamylamine and 1 month after stopping mecamylamine. CONCLUSIONS: This study suggested that administration of topical mecamylamine, a nonspecific nACh receptor blocker, may have heterogeneous effects in patients with diabetic macular edema. Variable expression of nACh receptor subtypes on endothelial cells that have different effects on permeability would provide an explanation for these results and should be investigated, because more specific nACh receptor blockers may dissociate antipermeability and propermeability effects. |
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Authors:
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Peter A Campochiaro; Syed Mahmood Shah; Gulnar Hafiz; Jeffery S Heier; Eugene S Lit; Ingrid Zimmer-Galler; Roomasa Channa; Quan Dong Nguyen; Beena Syed; Diana V Do; Lili Lu; James Monk; John P Cooke; M Ken Kengatharan; Henry H Hsu |
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Publication Detail:
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Type: Clinical Trial, Phase I; Clinical Trial, Phase II; Journal Article; Multicenter Study; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-02-26 |
Journal Detail:
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Title: American journal of ophthalmology Volume: 149 ISSN: 1879-1891 ISO Abbreviation: Am. J. Ophthalmol. Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-04-19 Completed Date: 2010-05-06 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 0370500 Medline TA: Am J Ophthalmol Country: United States |
Other Details:
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Languages: eng Pagination: 839-51.e1 Citation Subset: AIM; IM |
Copyright Information:
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Copyright 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-9277, USA. pcampo@jhmi.edu |
| Data Bank Information | |
Bank Name/Acc. No.:
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ClinicalTrials.gov/NCT00536692 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Administration, Topical Adolescent Adult Aqueous Humor / metabolism Chronic Disease Diabetic Retinopathy / drug therapy* Enzyme-Linked Immunosorbent Assay Fluorescein Angiography Fovea Centralis / pathology Humans Intraocular Pressure / physiology Macular Edema / drug therapy* Mecamylamine / administration & dosage*, adverse effects Nicotinic Antagonists / administration & dosage*, adverse effects Tomography, Optical Coherence Treatment Outcome Vascular Endothelial Growth Factor A / metabolism Visual Acuity / physiology |
| Grant Support | |
ID/Acronym/Agency:
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R01 CA098303/CA/NCI NIH HHS; R01 CA098303-04/CA/NCI NIH HHS; R01 EY012609/EY/NEI NIH HHS; R01 EY012609-10/EY/NEI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Nicotinic Antagonists; 0/VEGFA protein, human; 0/Vascular Endothelial Growth Factor A; 60-40-2/Mecamylamine |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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