- Количество слайдов: 11
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
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
Background • Only recently the FDA approved colchicine for the systemic treatment of FMF and gout.
Background • 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
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.
Cases Case Age/sex 1 79/M 2 Indication for colchicine Rx Clinical findings Initial Rx Culture results Response to conventional Rx Following discontinuation of Colchicine Gout Deep corneal ulcer in rt. Eye Fortified Garamycin and Cefamezin Systemic Tetracycline Topical steroids Staph. hominis No improvement Dramatic improvement and complete resolution 86/W Rheumatoid Arthritis Round central trophic ulcer 2/3 of corneal thickness Topical Gentamycin negative No improvement Complete epithelialization after 8 days 3 67/W Mixed connective tissue disease Peripheral corneal ulcer in the left eye with microperforation Chloramphenicol and Gentamycin negative No improvement Perforation sealed spontaneously and wound healed completely after 1 month 4 73/M FMF Superficial corneal ulcer in periphery 3 wks. Post cataract surgery Fortified Garamycin and Cefamezin negative No improvement Complete epithelialization and resolution after 4 days
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
Discussion • 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 • 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 • 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.
Bibliography 1. 2. 3. 4. 5. 6. Molad Y. Update on colchicine and its mechanism of action Curr Rheumatol Rep 2002; 4(3): 252 -6 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 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 Chvapil M, Peacock EE Jr, Carlson EC et al. Colchicine and wound healing. J Surg Res. 1980 Jan; 28(1): 49 -56. Olsen EG, Davanger M. Influence of colchicine on the healing of corneal endothelium. Acta Ophthalmol (Copenh). 1985 Apr; 63(2): 226 -31. 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.