Impaired Corneal Wound Healing in Patients on Systemic Colchicine

Moshe Lazar MD1, Yossi Yatziv MD1

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

• 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

Background

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.

CasesCaseAge/sexIndication for

colchicine RxClinical findingsInitial RxCulture resultsResponse to

conventional Rx

Following discontinuation

of Colchicine

179/MGoutDeep corneal ulcer in rt. Eye

Fortified Garamycin and Cefamezin

Systemic Tetracycline

Topical steroids

Staph. hominisNo improvement

Dramatic improvement and complete resolution

286/WRheumatoid Arthritis

Round central trophic ulcer 2/3 of corneal thickness

Topical Gentamycin

negativeNo improvement

Complete epithelialization after 8 days

367/WMixed connective tissue disease

Peripheral corneal ulcer in the left eye with microperforation

Chloramphenicol and Gentamycin

negativeNo improvement

Perforation sealed spontaneously and wound healed completely after 1 month

473/MFMFSuperficial corneal ulcer in periphery 3 wks. Post cataract surgery

Fortified Garamycin and Cefamezin

negativeNo 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

• 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.

Discussion

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.