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Long-term Administration of Topical Interferon Alfa-2 in the Treatment of Conjunctival Squamous Papilloma

Arch Ophthalmol. 2003;121:1052-1053.

Interferon alfa-2 is a well-known antiviral therapy with potent antiproliferative properties. Presumably, this has been the basis for its intralesional and short-term topical administration for squamous papillomas. Like other modalities used to treat these lesions, recurrence has been common with interferon therapy. However, recent evidence suggests that long-term administration of interferon alfa-2 is capable of inhibiting angiogenesis. Clinically, it has been used in this manner, for an 8-month duration, to successfully treat various vascular tumors such as hemanigomas, Kaposi sarcoma, and hemangiopericytomas¹ as well as ocular surface neoplasia.² We report the use of long-term topical therapy (8 months) with interferon alfa-2 in the successful treatment of recurrent squamous papilloma.

Report of a Case
A 27-year-old, healthy, white man complained of an enlarging itchy "lump" in the corner of his right eye. The patient had no significant medical history. His best-corrected visual acuity was 20/15 OU. Surrounding adnexa were unremarkable and there were no signs of adenopathy. A 3.7 x 2.8-mm sessile lesion consistent with a squamous papilloma (Figure 1) was identified in the medial canthal region. His anterior chamber and dilated fundus examination findings were also within normal limits.

View larger version (68K): [in this window] [in a new window] A, A 35-mm photograph of the right eye in right gaze, demonstrating a medial canthal lesion. B, A 35-mm photograph of the medial canthal region of the right eye demonstrating a squamous papilloma prior to treatment with interferon alfa-2. C, Digital photograph taken at the 1-year follow-up visit after the interferon alfa-2 treatment demonstrating total resolution of the squamous papilloma in the right eye,.

After informed consent was obtained, the patient was treated with a total of 0.3 mL (6 mIU/mL) of interferon alfa-2 (Intron-A; Schering, Kenilworth, NJ) subconjunctivally and intralesionally. He was then placed on a regimen of topical interferon alfa-2 at a concentration of 1 mIU/mL administered 4 times a day. Prompt regression of the lesion was noted at the patient's 2-week follow-up appointment. Topical therapy was stopped. At the 6-week follow-up, a recurrence of the squamous papilloma was observed. Additional subconjunctival and intralesional injections were administered. Topical therapy was reinstituted 4 times a day for a total of 8 months. By the 6-week follow-up the tumor had regressed. At 8 months, treatment with the eyedrops was discontinued and the patient remained tumor free. There remains no sign of recurrence at the 18-month follow-up appointment. Complete examinations were performed at each visit and included visual acuity, slitlamp, intraocular pressure, and dilated fundus evaluations. The patient experienced no apparent local or systemic side effects related to this therapeutic regimen.

Comment
Conjunctival squamous papillomas are composed of a fibrovascular core surrounded by an acanthotic squamous epithelium.³ There remains a strong association with the human papilloma virus, specifically, types 6, 11, and 16.

Management of these lesions is often difficult and can be frustrating for both patients and physicians. Surgical excision, cryotherapy, CO₂ laser ablation, mitomycin C, cimetidine, and acute interferon alfa-2 therapy have all been used. A recent article by Hawkins et al⁴ served as our source for the concentrations of the interferon alfa-2. They describe the acute resolution of the tumor with this modality but the need for mitomycin C for more permanent treatment.⁴ Unfortunately, despite the initial beneficial effects of most treatments, recurrence after cessation of therapy has been a noted outcome.

Interferon alfa-2 is traditionally known for its antiviral and antiproliferative properties. When given as long-term treatment, it has also been shown to possess antiangiogenic effects. Dinney et al¹ studied these effects on transitional cell carcinoma. Inhibition of angiogenesis was found to be highly associated with the decrease in basic fibroblastic growth factor and, theoretically, was responsible for the inhibition of tumor growth. A similar process may account for the inhibition of recurrence of the squamous papilloma in our patient.

Topical interferon has been successful in treating conjunctival papillomas in 2 patients.⁵ These patients received topical interferon alfa-2 at a dose of 1 mIU/mL 4 times a day until there was complete regression.⁵ Successful treatment of recurrent lacrimal papilloma with topical and intralesional injection has also been reported.⁶ In addition, there are 2 case series that document resolution of conjunctival and corneal intraepithelial neoplasia with topical⁷ and perilesional injection and topical interferon alfa-2.² These investigators also used a topical dose of 1 mIU/mL but only continued therapy until the lesion was not clinically detectable.^{1, 7}

We believe that the long-term use of topical therapy in the treatment of squamous papilloma may take advantage of the compound's antiangiogenic properties and therefore prevent recurrence. It appears to be a safe and effective treatment for this tumor. The exact mechanism by which long-term therapy with inteferon alfa-2 may exhibit its effects needs further study.

AUTHOR INFORMATION

Kenneth E. Morgenstern, MD; Jason Givan, MS; Lee A. Wiley, MD
Morgantown, WVa

Corresponding author and reprints: Lee A. Wiley, MD, Department of Ophthalmology, West Virginia University School of Medicine, PO Box 9193, Morgantown, WV 26506 (e-mail: lwiley{at}hsc.wvu.edu).

REFERENCES
1. Dinney CP, Bielenberg DR, Perrotte P, et al. Inhibition of basic fibroblast growth factor expression, angiogenesis, and growth of human bladder carcinoma in mice by systemic interferon- administration. Cancer Res. 1998;58:808-814. FREE FULL TEXT 2. Vann Robin R, Karp CL. Perilesional and topical interferon 2 for conjunctival and corneal neoplasia. Ophthalmology. 1999;106:91-97. FULL TEXT | ISI | PUBMED 3. Sjo N, Heegaard S, Prause JU. Conjunctival papilloma: a histopathologically based retrospective study. Acta Ophthalmol Scand. 2000;78:663-666. FULL TEXT | PUBMED 4. Hawkins AS, Yu J, Hamming NA, Rubenstein JB. Treatment of recurrent conjunctival papillomatosis with mitomycin C. Am J Ophthalmol. 1999;128:638-640. FULL TEXT | PUBMED 5. Schechter BA, Rand WJ, Velazquez GE, Williams WD, Starasoler L. Treatment of conjunctival papillomata with topical interferon 2. Am J Ophthalmol. 2002;134:268-270. PUBMED 6. Parulekar MV, Khooshabeh R, Graham C. Topical and intralesional interferon therapy for recurrent lacrimal papilloma. Eye. 2002;16:649-651. PUBMED 7. Karp CL, Moore JK, Rosa RH. Treatment of conjunctival and corneal intraepithelial neoplasia with topical interferon 2. Ophthalmology. 2001;108:1093-1097. FULL TEXT | ISI | PUBMED

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