Topical Mecamylamine for Diabetic Macular Edema

Campochiaro, Peter A.; Shah, Syed Mahmood; Hafiz, Gulnar; Heier, Jeffery S.; Lit, Eugene S.; Zimmer-Galler, Ingrid; Channa, Roomasa; Nguyen, Quan Dong; Syed, Beena; Do, Diana V.; Lu, Lili; Monk, James; Cooke, John P.; Kengatharan, M. Ken; Hsu, Henry H.

doi:10.1016/j.ajo.2009.12.005

« Previous Next »American Journal of Ophthalmology
Volume 149, Issue 5 , Pages 839-851.e1, May 2010

Topical Mecamylamine for Diabetic Macular Edema

Peter A. Campochiaro
- Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland
- Inquiries to Peter A. Campochiaro, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Maumenee 719, Baltimore, MD 21287-9277
Syed Mahmood Shah
- Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland
Gulnar Hafiz
- Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland
Jeffery S. Heier
- Ophthalmic Consultants of Boston, Boston, Massachusetts
Eugene S. Lit
- East Bay Retina Consultants, Boston, Massachusetts
Ingrid Zimmer-Galler
- Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland
Roomasa Channa
- Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland
Quan Dong Nguyen
- Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland
Beena Syed
- Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland
Diana V. Do
- Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland
Lili Lu
- Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland
James Monk
- CoMentis, Inc, South San Francisco, California
John P. Cooke
- Division of Cardiovascular Medicine, Stanford University, Palo Alto, California
M. Ken Kengatharan
- CoMentis, Inc, South San Francisco, California
Henry H. Hsu
- CoMentis, Inc, South San Francisco, California

Accepted 1 December 2009. published online 26 February 2010.

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.