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Surgical excision, autolimbal transplantation, and mitomycin C in the treatment of conjunctival and corneal intraepithelial neoplasia
  1. ANNIE JOSEPH,
  2. KOURESH SABRI,
  3. HARMINDER S DUA
  1. Department of Ophthalmology, University Hospital, Queen's Medical Centre, Nottingham NG7 2UH, UK
  1. harminder.dua{at}nottingham.ac.uk

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Editor,—Conjunctival and corneal intraepithelial neoplasia (CIN) are uncommon lesions of low malignant potential.1 Surgical excision is the standard treatment for this condition. However, owing to the poorly defined borders of these lesions, recurrence rates following surgical excision can be as high as 53%.2 Adjunctive therapy including cryotherapy,3 radiotherapy,4immunotherapy,5 and topical alcohol and urea have been used to treat the condition. Many of these procedures induce limbal stem cell failure with consequent corneal epithelial problems, requiring (auto) stem cell transplantation. Topical cytotoxic agents like 5-fluorouracil and mitomycin C have been used successfully in the treatment of CIN.6 However, inhibition of limbal stem cell division with mitomycin C is thought to notably impair physiological corneal epithelial replacement.7 We report the successful use of prolonged mitomycin C after autolimbal transplantation in the treatment of recurrent CIN.

CASE REPORT

A 37 year old white woman presented in February 1995 with a 6 month history of a fleshy white lesion in the corner of her right eye. In the past she had experienced intermittent episodes of bilateral sore, red eyes. Her visual acuities were 6/18 with pinhole in the right eye and 6/5 in the left eye. Ocular examination revealed a whitish elevated lesion on the right limbal conjunctiva from 7 to 11 o'clock extending almost to the central cornea (Fig 1A).

Figure 1

(A) Pretreatment view of right eye showing conjunctival/corneal intraepithelial neoplasia (CIN). (B) Photomicrograph of the initial biopsy specimen showing the features of CIN (stain haematoxylin and eosin; original magnification, ×100). (C) Recurrence of CIN after autologous limbal transplantation. (D) The lesion has not recurred 20 months after mitomycin C therapy. Arrows show the two areas of autologous limbal transplantation.

The patient underwent excision biopsy of the lesion. Intraoperatively the exposed bed of the lesion was treated with absolute alcohol and the conjunctival edge with two cycles of cryotherapy. Postoperatively, a bandage contact lens was inserted and she was treated with topical preservative-free antibiotics and steroids. One month later the corneal and conjunctival epithelium had healed completely and vision improved to 6/12. Histology confirmed the lesion to be conjunctival and corneal intraepithelial neoplasia (Fig 1B).

Two months postoperatively, she developed a recurrence in the form of two central, abnormal areas of corneal epithelium. These were treated by scraping and application of absolute alcohol to the bed of the lesion. Histology identified these lesions to be severely dysplastic corneal epithelial cells. Subsequently she developed right limbal stem cell failure resulting in recurrent episodes of filamentary and punctate keratitis and a reduction of visual acuity to 6/18. Histology of corneal scrapes showed epithelial cells and goblet cells. In February 1998 she underwent a right autologous limbal transplant and vision improved to 6/9.

Two months later she had a recurrence of CIN involving one third of the cornea (Fig 1C). This was treated with four cycles of 0.04% mitomycin C applied four times a day, for 10 days at a time. The tumour regressed completely in 3 months. Twenty months later she remains asymptomatic with a clear cornea (Fig 1D).

COMMENT

Mitomycin C is a cytotoxic alkylating agent which inhibits DNA synthesis and is, therefore, most effective against rapidly dividing cells. While it has been used to treat recurrences of CIN, there have been concerns about the effects of mitomycin C on the limbal stem cells and the integrity of the corneal epithelium.7 In our patient the grafted limbal stem cells and corneal epithelium remained healthy in spite of the significant dose of mitomycin C required to treat her recurrent CIN. To the best of our knowledge this is the first reported case of topical mitomycin C used successfully against CIN after autolimbal transplant, despite the prolonged duration of application (40 days).

Acknowledgments

The authors would like to thank Miss April Powell-Richards and Professor J Lowe for their help with the illustrations.

References

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