Topical mecamylamine for diabetic macular edema.
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.
Campochiaro
Peter A
PA
Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-9277, USA. pcampo@jhmi.edu
Shah
Syed Mahmood
SM
Hafiz
Gulnar
G
Heier
Jeffery S
JS
Lit
Eugene S
ES
Zimmer-Galler
Ingrid
I
Channa
Roomasa
R
Nguyen
Quan Dong
QD
Syed
Beena
B
Do
Diana V
DV
Lu
Lili
L
Monk
James
J
Cooke
John P
JP
Kengatharan
M Ken
MK
Hsu
Henry H
HH
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
D018733:Nicotinic Antagonists; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D008464:Mecamylamine