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Corneal epithelial dysplasia after trifluridine use

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Abstract

Prolonged topical trifluridine treatment of herpes simplex keratitis in three elderly patients produced slightly raised dysplastic corneal epithelial lesions. The involved epithelium had a ground-glass appearance and exhibited opaque cells, edema, and spindle-shaped surface cells. Histopathology demonstrated severe cellular atypism, loss of cell polarity, dyskeratosis, parakeratosis, and a few mitotic figures. The pathological change was apparently intraepithelial. After scraping, the edema and opaque cells in the regenerated epithelium gradually disappeared in 3–4 months on cessation of trifluridine therapy. In one patient recurrence of dendritic keratitis, 5 weeks after scraping, was treated by topical bromovinyldeoxyuridine eye drops. Since severe epithelial dysplasia may represent a precancerous condition, prolonged use of trifluridine should be avoided.

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References

  • Aebersold PM (1979) Relative mutagenicity of nucleoside virostatic drugs in Chinese hamster ovary cells. Adv Ophthalmol 38: 241

    Google Scholar 

  • Apple DJ, Rabb MF (1978) Clinicopathological correlation of ocular disease. A text and stereoscopic atlas. C.V. Mosby Company, St. Louis, p. 77

    Google Scholar 

  • Brewitt H, Feuerhake C (1981) The effect of trifluorothymidine on epithelial wound healing in rabbit cornea. A scanning electron microscopic study. In: Sundmacher R (ed): Herpetic Eye Diseases. J.F. Bergman Verlag, München, p 277

    Google Scholar 

  • Campbell RJ, Bourne WM (1981) Unilateral central corneal dysplasia. Ophthalmology 88: 1231

    CAS  PubMed  Google Scholar 

  • Carrano AV, Thompson LH, Lindl PA, Minkler JL (1978) Sister chromatid exchanges as an indicator of mutagenesis. Nature 271: 551

    Article  CAS  PubMed  Google Scholar 

  • Cassiman JJ, De Clercq E, Jones AS, Walker RT, Van den Berghe H (1981) Sister chromatid exchange induced by anti-herpes drugs. Br Med J 283: 817

    CAS  Google Scholar 

  • Coster DJ, McKinnon JR, McGill JI, Jones BR, Fraunfelder FT (1976) Clinical evaluation of adenine arabinoside and trifluorothymidine in the treatment of corneal ulcers caused by herpes simplex virus. J Infect Dis 113 (Suppl 1): A173

    Google Scholar 

  • Coster DJ, Jones BR, McGill JI (1979) Treatment of amoeboid herpetic ulcers with adenine arabinoside or trifluorothymidine. Br J Ophthalmol 63: 418

    CAS  PubMed  Google Scholar 

  • Crawford JB (1981) Conjunctival tumors. In: Duane TD (ed): Clinical Ophthalmology, vol 4. Harper and Row, Philadelphia. p 1

    Google Scholar 

  • De Clercq E, Descamps J, Barr PJ, Jones AS, Serafinowski P, Walker RT, Huang GF, Torrence PF, Schmidt CL, Mertes MP, Kulikowski T, Shugar D (1979a) Comparative study of the potency and selectivity of antiherpes compounds. In: Skoda J and Langen P (eds): Antimetabolites in Biochemistry, Biology and Medicine. Pergamon Press, New York, p 275

    Google Scholar 

  • De Clercq E, Descamps J, De Somer P, Barr PJ, Jones AS, Walker RT (1979b) (E)-5-(2-Bromovinyl)-2′-deoxyuridine: a potent and selective antiherpes agent. Proc Natl Acad Sci USA 76: 2947

    Google Scholar 

  • De Clercq E, Descamps J, Verhelst G, Walker RT, Jones AS, Torrence PF, Shugar D (1980a) Comparative efficacy of different antiherpes drugs against different strains of herpes simplex virus. J Infect Dis 141: 563

    Google Scholar 

  • De Clercq E, De Greef H, Wildiers J, De Jonge G, Drochmans A, Descamps J, De Somer P (1980b) Oral (E)-5-(2-bromovinyl)-2′-deoxyuridine in severe herpes zoster. Br Med J 281: 1178

    Google Scholar 

  • De Clercq E, Heremans H, Descamps J, Verhelst G, De Ley M, Billiau A (1981) Effects ofE-5-(2-bromovinyl)-2′-deoxyuridine and other selective anti-herpes compounds on the induction of retrovirus particles in mouse BALB/3T3 cells. Mol Pharmacol 19: 122

    PubMed  Google Scholar 

  • Duke-Elder S, Leigh AG (1965) In: Duke-Elder S (ed): System of Ophthalmology. Diseases of the Outer Eye. Vol. VIII, Part 2. Henry Kimpton, London, p 661

    Google Scholar 

  • Erbakhan S, Aksu Y, Slem G (1963) Bowen's disease. Report of two cases. Am J Ophthalmol 55: 620

    Google Scholar 

  • Falcon MG, Jones BR, Williams HP, Coster DJ (1977) Management of herpetic eye disease. Trans Ophthalmol Soc UK 97: 345

    CAS  PubMed  Google Scholar 

  • Falcon MG, Jones BR, Williams HP, Wilhelmus K, Coster DJ (1981) Adverse reactions in the eye from topical therapy with idoxuridine, adenine arabinoside and trifluorothymidine. In: Sundmacher R (ed): Herpetic Eye Diseases. J.F. Bergman Verlag, München, p 263

    Google Scholar 

  • Foster CS, Pavan-Langston D (1977) Corneal wound healing and antiviral medication. Arch Ophthalmol 95: 2062

    CAS  PubMed  Google Scholar 

  • Gasset AR, Katzin D (1975) Antiviral drugs and corneal wound healing. Invest Ophthalmol Vis Sci 14: 628

    CAS  Google Scholar 

  • Gottschling H, Heidelberger C (1963) Fluorinated pyrimidines. XIX. Some biological effects of 5-trifluoromethyluracil and 5-trifluoromethyl-2′-deoxyuridine on Escherichia coli and bacteriophage T4B. J Mol Biol 7: 541

    CAS  Google Scholar 

  • Heidelberger C (1975) Fluorinated pyrimidines and their nucleosides. In: Sartorelli AC and Johns DG (eds): Handbook of Experimental Pharmacology. Antineoplastic and Immunosuppressive Agents. Part 11. Springer-Verlag, New York, p 193

    Google Scholar 

  • Hogan MJ, Zimmerman LE (1962) Ophthalmic Pathology. An Atlas and Textbook. W.B. Saunders Co, Philadelphia, p 252

    Google Scholar 

  • Irvine AR Jr (1967) Diffuse epibulbar squamous-cell epithelioma. Am J Ophthalmol 64: 550

    PubMed  Google Scholar 

  • Itoi M, Gefter JW, Kaneko N, Ishii Y, Ramer RM, Gasset AR (1975) Teratogenicities of ophthalmic drugs. I. Antiviral ophthalmic drugs. Arch Ophthalmol 93: 46

    CAS  PubMed  Google Scholar 

  • Jones PA, Benedict WF, Baker MS, Mondal S, Rapp U, Heidelberger C (1976) Oncogenic transformation of C3H/10T1/2 clone 8 mouse embryo cells by halogenated pyrimidine nucleosides. Cancer Res 36: 101

    CAS  PubMed  Google Scholar 

  • Kury G, Crosby RJ (1967) The teratogenic effect of 5-trifluoromethyl-2′-deoxyuridine in chicken embryos. Toxicol Appl Pharmacol 11: 72

    CAS  PubMed  Google Scholar 

  • Laibson PR, Arentsen JJ, Mazzanti WD, Eiferman RA (1977) Double controlled comparison of IDU and trifluorothymidine in 33 patients with superficial herpetic keratitis. Trans Am Ophthalmol Soc 75: 316

    CAS  PubMed  Google Scholar 

  • Locke JC (1956) Bowen's disease (intraepithelial epithelioma) of the cornea and conjunctiva. A clinicopathologic study. Am J Ophthalmol 41: 801

    CAS  PubMed  Google Scholar 

  • Maudgal PC, Missotten L (1977a) La réplique de la cornée appliquée a l'étude de la kératite herpétique. Bull Soc Belge Ophthalmol 175: 26

    Google Scholar 

  • Maudgal PC, Missotten L (1977b) Development of disseminating inclusion bodies in experimental herpes simplex keratitis. Bull Soc Belge Ophthalmol 179: 25

    CAS  Google Scholar 

  • Maudgal PC (1978) The epithelial response in keratitis sicca and keratitis herpetica (an experimental and clinical study). Doc Ophthalmol 45: 223

    Article  CAS  PubMed  Google Scholar 

  • Maudgal PC, Missotten L (1978a) Cytology of the superficial keratinised cells in experimental keratitis sicca. Ophthalmologica 196: 113

    Google Scholar 

  • Maudgal PC, Missotten L (1978b) Histopathology of the human superficial herpes simplex keratitis. Br J Ophthalmol 62: 46

    CAS  Google Scholar 

  • Maudgal PC, De Clercq E, Descamps J, Missotten L (1979) Comparative evaluation of BVDU ((E)-5-(2-bromovinyl)-2′-deoxyuridine) and IDU (5-iodo-2′-deoxyuridine) in the treatment of experimental herpes simplex keratitis in rabbits. Bull Soc Belge Ophthalmol 186: 109

    CAS  Google Scholar 

  • Maudgal PC, Missotten L (1979a) Histopathological study of the human herpes simplex denderitic and punctate keratitis by replica technique. Doc Ophthalmol Proc Series 20: 211

    Google Scholar 

  • Maudgal PC, Missotten L (1979b) Histopathology and histochemistry of the superficial corneal epithelium in experimental herpes simplex keratitis. Albrecht von Graefes Arch Klin Exp Ophthalmol 209: 239

    Article  CAS  Google Scholar 

  • Maudgal PC, De Clercq E, Descamps J, Missotten L, De Somer P, Busson R, Vanderhaeghe H, Verhelst G, Walker RT, Jones AS (1980) (E)-5-(2-Bromovinyl)-2′-deoxyuridine in the treatment of experimental herpes simplex keratitis. Antimicrob Agents Chemother 17: 8

    CAS  PubMed  Google Scholar 

  • Maudgal PC, Missotten L (1980) Superficial keratitis. Monographs in Ophthalmology 1. W. Junk b.v. Publishers, Boston

    Google Scholar 

  • Maudgal PC, Dralands L, Lamberts L, De Clercq E, Descamps J, Missotten L (1981a) Preliminary results of oral BVDU treatment of herpes zoster ophthalmicus. Bull Soc Belge Ophthalmol 193: 49

    CAS  Google Scholar 

  • Maudgal PC, Missotten L, De Clercq E, Descamps J, De Meuter E (1981b) Efficacy of (E)-5-(2-bromovinyl)-2′-deoxyuridine in the topical treatment of herpes simplex keratitis. Albrecht von Graefes Arch Klin Exp Ophthalmol 216: 261

    CAS  Google Scholar 

  • Maudgal PC, De Clercq E, Descamps J, Missotten L, Wijnhoven J (1982a) Experimental stromal herpes simplex keratitis. Influence of treatment with topical bromovinyldeoxyuridine and trifluridine. Arch Ophthalmol 100: 653

    CAS  Google Scholar 

  • Maudgal PC, Uyttebroeck W, De Clercq E, Missotten L (1982b) Oral and topical treatment of experimental herpes simplex iritis with bromovinyldeoxyuridine. Arch Ophthalmol 100: 1337

    CAS  Google Scholar 

  • McGavic JS (1942) Intraepithelial epithelioma of the cornea and conjunctiva (Bowen's disease). Am J Ophthalmol 25: 167

    Google Scholar 

  • McGill J, Holt-Wilson AD, McKinnon JR, Williams HP, Jones BR (1974) Some aspects of the clinical use of trifluorothymidine in the treatment of herpetic ulceration of the cornea. Trans Ophthalmol Soc U K 94: 342

    Google Scholar 

  • Missotten L, Maudgal PC (1977) The replica technique used to study the superficial corneal epithelium in vivo. Am J Ophthalmol 84: 104

    CAS  PubMed  Google Scholar 

  • Parkhurst JR, Danenberg PV, Heidelberger C (1976) Growth inhibition of cells in culture and of vaccinia virus infected HeLa cells by derivatives of trifluorothymidine. Chemotherapy 22: 221

    CAS  PubMed  Google Scholar 

  • Pavan-Langston D, Foster CS (1977) Trifluorothymidine and idoxuridine therapy of ocular herpes. Am J Ophthalmol 84: 818

    CAS  PubMed  Google Scholar 

  • Pizzarello LD, Jakobiec FA (1978) Bowen's disease of the conjunctiva: a misnomer. In: Jakobiec FA (ed): Ocular and Adnexal Tumors. Aesculapius Publishing Co, Birmingham, p 553

    Google Scholar 

  • Prusoff WH (1981) Development of antiviral drugs. In: Sundmacher R (ed): Herpetic Eye Diseases. J.F. Bergmann Verlag, München, p 223

    Google Scholar 

  • Reese AB (1976) Tumors of the Eye. Harper and Row, Hagerstown, p 56

    Google Scholar 

  • Sugar J, Stark W, Binder PS, Meyer R, Chandler JW, Waring GO, Hirst L, King DH (1980) Trifluorothymidine treatment of herpes simplex epithelial keratitis and comparison with idoxuridine. Annals Ophthalmol 12: 611

    Google Scholar 

  • Taylor JL, O'Brien WJ (1981) The cytotoxicity of nucleoside antivirals to epithelial cells of ocular origin. In: Sundmacher R (ed): Herpetic Eye Diseases. J.F. Bergman Verlag, München, p 269

    Google Scholar 

  • Tripathi RC, Garner A (1972) The ultrastructure of preinvasive cancer of the corneal epithelium. Cancer Res 32: 90

    CAS  PubMed  Google Scholar 

  • Umeda M, Heidelberger C (1968) Comparative studies of fluorinated pyrimidines with various cell lines. Cancer Res 28: 2529

    CAS  PubMed  Google Scholar 

  • Van Bijsterveld OP, Host H (1980) Trifluorothymidine versus adenine arabinoside in the treatment of herpes simplex keratitis. Br J Ophthalmol 64: 33

    PubMed  Google Scholar 

  • Yanoff M, Fine BS (1975) Ocular Pathology. A Text and Atlas. Harper and Row, Hagerstown, p 277

    Google Scholar 

  • Zimmerman LE (1964) Squamous cell carcinoma and related lesions of the bulbar conjunctiva. In: Boniuk M (ed): Ocular and Adnexal Tumors. New and Controversial Aspects. C.V. Mosby, St. Louis, p 49

    Google Scholar 

  • Zimmerman LE (1969) The cancerous, precancerous and pseudocancerous lesions of the cornea and conjunctiva. In: Raycroft PV (ed): Corneoplastic Surgery. Pergamon Press, Osford, p 547

    Google Scholar 

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Authors and Affiliations

  1. Eye Research Laboratory of the Ophthalmology Clinic, University of Leuven, B-3000, Leuven, Belgium

    P. C. Maudgal & L. Missotten

  2. Pathology Department, University of Leuven, B-3000, Leuven, Belgium

    B. Van Damme

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  1. P. C. Maudgal
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  2. B. Van Damme
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  3. L. Missotten
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Maudgal, P.C., Van Damme, B. & Missotten, L. Corneal epithelial dysplasia after trifluridine use. Graefe's Arch Clin Exp Ophthalmol 220, 6–12 (1983). https://doi.org/10.1007/BF02307009

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