Topical Mecamylamine for Diabetic Macular Edema

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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Abstract

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.

Original languageEnglish (US)
Pages (from-to)839-851.e1
JournalAmerican journal of ophthalmology
Volume149
Issue number5
DOIs
StatePublished - May 2010

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Mecamylamine
Macular Edema
Nicotinic Receptors
Visual Acuity
Endothelial Cells
Safety
Topical Administration
Phase II Clinical Trials
Clinical Trials, Phase I
Optical Coherence Tomography
Capillary Permeability
Patient Safety
Permeability
Animal Models
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Campochiaro, P. A., Shah, S. M., Hafiz, G., Heier, J. S., Lit, E. S., Zimmer-Galler, I., ... Hsu, H. H. (2010). Topical Mecamylamine for Diabetic Macular Edema. American journal of ophthalmology, 149(5), 839-851.e1. https://doi.org/10.1016/j.ajo.2009.12.005

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.

In: American journal of ophthalmology, Vol. 149, No. 5, 05.2010, p. 839-851.e1.

Research output: Contribution to journalArticle

Campochiaro, PA, Shah, SM, Hafiz, G, Heier, JS, Lit, ES, Zimmer-Galler, I, Channa, R, Nguyen, QD, Syed, B, Do, DV, Lu, L, Monk, J, Cooke, JP, Kengatharan, MK & Hsu, HH 2010, 'Topical Mecamylamine for Diabetic Macular Edema', American journal of ophthalmology, vol. 149, no. 5, pp. 839-851.e1. https://doi.org/10.1016/j.ajo.2009.12.005
Campochiaro PA, Shah SM, Hafiz G, Heier JS, Lit ES, Zimmer-Galler I et al. Topical Mecamylamine for Diabetic Macular Edema. American journal of ophthalmology. 2010 May;149(5):839-851.e1. https://doi.org/10.1016/j.ajo.2009.12.005
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. / Topical Mecamylamine for Diabetic Macular Edema. In: American journal of ophthalmology. 2010 ; Vol. 149, No. 5. pp. 839-851.e1.
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AU - Lit, Eugene S.

AU - Zimmer-Galler, Ingrid

AU - Channa, Roomasa

AU - Nguyen, Quan Dong

AU - Syed, Beena

AU - Do, Diana V.

AU - Lu, Lili

AU - Monk, James

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AU - Kengatharan, M. Ken

AU - Hsu, Henry H.

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