Transcript 582: Impaired Corneal Wound Healing in Patients on Systemic

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
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.