1. Impaired Corneal Wound Healing in Patients on Systemic Colchicine Moshe Lazar MD 1, Yossi Yatziv MD 1 The authors have no financial interest in the subject of this poster 1 Tel Aviv Medical Center, Israel

2. Background Colchicine is a systemic anti-inflammatory drug used for the long term treatment of Familial Mediterranean Fever (FMF), Behcet’s disease, Rheumatoid Arthritis, Gout and other diseases. Colchicine is known to prevent activation of neutrophils and inhibit mitotic spindle formation. It modulates chemokines, prostanoids production and inhibits endothelial cell adhesion molecules. 1,2

3. Only recently the FDA approved colchicine for the systemic treatment of FMF and gout. Background

4. Delay in corneal wound healing in patients treated with colchicine was previously reported by Biedner et. al. who described two cases of healing suppression in corneal dellen after strabismus surgery. 3 Background

5. Methods & Patients We present a series of four patients, all under systemic colchicine who presented with corneal ulcers unresponsive to treatment with topical antibiotics. Cessation of colchicine treatment resulted in resolution of the corneal ulcer in all cases.

6. Cases Following discontinuation of Colchicine Response to conventional Rx Culture resultsInitial RxClinical findingsIndication for colchicine Rx Age/sexCase Dramatic improvement and complete resolution No improvement Staph. hominisFortified Garamycin and Cefamezin Systemic Tetracycline Topical steroids Deep corneal ulcer in rt. Eye Gout79/M1 Complete epithelialization after 8 days No improvement negativeTopical Gentamycin Round central trophic ulcer 2/3 of corneal thickness Rheumatoid Arthritis 86/W2 Perforation sealed spontaneously and wound healed completely after 1 month No improvement negativeChloramphenicol and Gentamycin Peripheral corneal ulcer in the left eye with microperforation Mixed connective tissue disease 67/W3 Complete epithelialization and resolution after 4 days No improvement negativeFortified Garamycin and Cefamezin Superficial corneal ulcer in periphery 3 wks. Post cataract surgery FMF73/M4

7. Discussion We described four similar cases of patients on colchicine Rx, unresponsive to conventional antibiotic treatment. Colchicine may adversely affect wound healing through its inhibitory effect on tubulin dependent cell functions and through collagenase activation. In some animal models and in vitro studies, colchicine was shown to inhibit epithelium and fibroblast mitosis, fibroblast migration, endothelial cell migration and collagen deposition. 4,5

8. Colchicine was demonstrated to be excreted in the tear fluid in patients on systemic Rx. 6 This may provide a possible route by which the drug may affect and inhibit healing of corneal ulcers. Discussion

9. We cannot establish a definite cause-effect relationship between colchicine and these corneal complications. However, in light of previous reports, the experimental data and the fact that all of our patients were unresponsive to conventional therapy while showing a dramatic resolution once colchicine was withdrawn, makes it reasonable to assume that the drug interfered with corneal healing Discussion

10. We suggest that in patients with corneal ulcers refractory to conventional treatment who are being treated with colchicine, cessation of colchicine treatment should be considered whenever possible. Discussion

11. Bibliography 1.Molad Y. Update on colchicine and its mechanism of action Curr Rheumatol Rep 2002;4(3):252-6 2.Cerquaglia C, Diaco M, Nucera G, et al. Pharmacological and clinical basis of treatment of Familial Mediterranian Fever (FMF) with colchicines and analogues: an update Curr Drug Targets Inflamm Allergy 2005;4:117-24 3.Biedner BZ, Rothkoff L, Friedman L, Geltman C. Colchicine suppression of corneal healing after strabismus surgery. Br J Ophthalmol. 1977 Jul;61(7):496-7 4.Chvapil M, Peacock EE Jr, Carlson EC et al. Colchicine and wound healing. J Surg Res. 1980 Jan;28(1):49-56. 5.Olsen EG, Davanger M. Influence of colchicine on the healing of corneal endothelium. Acta Ophthalmol (Copenh). 1985 Apr;63(2):226-31. 6.Leibovitch I, Alster Y, Scherrmann JM et al. Colchicine in tear fluid of treated patients with familial Mediterranean fever. Cornea. 2003 Apr;22(3):191-3.