1 Tel-Aviv Medical Center, Ophthalmology, Tel-Aviv and
2 Sheba Medical Center, Tel-Hashomer, The Heller Institute of Medical Research, Ramat Gan, Israel
SIR, Colchicine is an anti-inflammatory drug used for the treatment of familial Mediterranean fever (FMF), Behcet's disease, rheumatoid arthritis, gout and other diseases. Experimental studies suggest that the drug may delay corneal wound healing [1, 2]. Beidner et al. [3] and Alster et al. [4] previously reported on four patients treated with colchicine who suffered from delay in corneal wound healing.
We present a patient with FMF, treated with colchicine, who underwent extracapsular cataract extraction (ECCE) with intraocular lens implantation and developed severe wound healing problems resulting in complete loss of vision in the operated eye. This report links colchicine to another possible delay in corneal healing.
A 55-yr-old man with recurrent episodes of peritonitis, pleuritis and arthritis, which were usually associated with fever and lasting from 1 to 4 days, was diagnosed as FMF about 30 yr ago. He had a younger brother with the same disease. He was treated with 2 mg colchicine daily. The patient underwent an ECCE with intraocular lens implantation. After the first three uneventful postoperative weeks, a large persistent corneal epithelial defect developed and the topical steroid treatment was stopped. The patient was treated by a pressure patch and then by a soft contact lens. This conventional treatment was unsuccessful. Perforation and melting of the cornea ensued, and the patient underwent a penetrating keratoplasty. Severe wound healing complications developed in the corneal graft, but two additional keratoplasties for graft melting were unsuccessful. All surgery was performed while the patient continued his colchicine treatment.
The patient was evaluated for local or systemic factors that could cause corneal melting, including keratoconjunctivitis sicca, Sjogren's syndrome, rheumatoid arthritis and Wegener's granulomatosis, but they were all serologically and clinically ruled out. There were no signs of dry eye or herpetic eye disease, and lid function was normal. There was no previous systemic steroidal, nonsteroidal anti-inflammatory, cytotoxic or immunosuppressive therapy.
After the third keratoplasty operation, secondary glaucoma developed, followed by a rapid deterioration in visual acuity and by phthisis with permanent visual loss.
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 [1, 2].
Beidner et al. [3] reported two patients treated with colchicine for FMF who underwent strabismus surgery. In the first patient, a postoperative corneal dellen persisted for 8 weeks, but recovered completely 3 days after stopping colchicine. The second patient was a young boy who had a corneal erosion that persisted for 3 weeks and which healed 2 days after colchicine was discontinued. We recently reported two patients on colchicine therapy for connective tissue disease with persistent corneal ulcers [4]. Both improved dramatically after withdrawal of the medication.
Corneal ulceration with rapidly progressive stromal thinning or melting occurs most commonly in association with a systemic vasculitis [5]. Corneal melting following ocular surgery is a very rare complication. The exact prevalence of this postoperative complication in the general population has not been determined. It is most frequently associated with pre-existing tear-film abnormalities resulting from keratoconjunctivitis sicca, Sjogren's syndrome and collagen vascular disease, especially rheumatoid arthritis and Wegener's granulomatosis [6]. None of these conditions was found in our patients.
In light of the four previously reported cases, and the extensive experimental evidence, it is reasonable to assume that colchicine altered the normal process of corneal wound healing, although there is no definite proof for this.
There are no reports of wound-healing complications in colchicine-treated patients after non-ocular surgical procedures, nor is there any recommendation to discontinue colchicine therapy before any surgery. In our opinion, this should be the rule regarding ocular surgery as well. This report certainly does not presume to establish a causal relationship between colchicine and defected corneal wound healing. However, in light of this and previously reported cases, we were prompted to send a word of caution on a possible link between colchicine and delayed wound healing.
Notes
Correspondence to: I. Leibovitch. E-mail: lleibo{at}bezeqint.net, photog{at}tasmc.health.gov.il
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