title: Topical mecamylamine for diabetic macular edema.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-9277, USA. pcampo@jhmi.edu
authors.forename: Peter A
authors.initials: PA
authors.lastname: Campochiaro
authors.forename: Syed Mahmood
authors.initials: SM
authors.lastname: Shah
authors.forename: Gulnar
authors.initials: G
authors.lastname: Hafiz
authors.forename: Jeffery S
authors.initials: JS
authors.lastname: Heier
authors.forename: Eugene S
authors.initials: ES
authors.lastname: Lit
authors.forename: Ingrid
authors.initials: I
authors.lastname: Zimmer-Galler
authors.forename: Roomasa
authors.initials: R
authors.lastname: Channa
authors.forename: Quan Dong
authors.initials: QD
authors.lastname: Nguyen
authors.forename: Beena
authors.initials: B
authors.lastname: Syed
authors.forename: Diana V
authors.initials: DV
authors.lastname: Do
authors.forename: Lili
authors.initials: L
authors.lastname: Lu
authors.forename: James
authors.initials: J
authors.lastname: Monk
authors.forename: John P
authors.initials: JP
authors.lastname: Cooke
authors.forename: M Ken
authors.initials: MK
authors.lastname: Kengatharan
authors.forename: Henry H
authors.initials: HH
authors.lastname: Hsu
mesh_terms: D000287:Administration, Topical; D000293:Adolescent; D000328:Adult; D001082:Aqueous Humor / Q000378:metabolism; D002908:Chronic Disease; D003930:Diabetic Retinopathy / Q000188:drug therapy*; D004797:Enzyme-Linked Immunosorbent Assay; D005451:Fluorescein Angiography; D005584:Fovea Centralis / Q000473:pathology; D006801:Humans; D007429:Intraocular Pressure / Q000502:physiology; D008269:Macular Edema / Q000188:drug therapy*; D008464:Mecamylamine / Q000008:administration & dosage* / Q000009:adverse effects; D018733:Nicotinic Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D041623:Tomography, Optical Coherence; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014792:Visual Acuity / Q000502:physiology
chemical_list: D018733:Nicotinic Antagonists; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D008464:Mecamylamine