Topical Interferon Alfa in the Treatment of Conjunctival Melanoma and Primary Acquired Melanosis Complex PAUL T. FINGER, RAGUI W. SEDEEK, AND KIMBERLY J. CHIN ● PURPOSE: To report on topical interferon alfa-2b for conjunctival malignant melanoma (CMM) and primary acquired melanosis with atypia (PAM). ● DESIGN: Retrospective, interventional case series. ● METHODS: Five eyes of five consecutive patients with biopsy-proven malignant melanoma were treated with topical interferon alfa-2b as treatment for primary or recurrent disease. One drop of interferon alfa-2b (1 million units/ml) was placed into the superior fornix four times daily for three months. Punctal plugs limited systemic absorption. The main outcome measure was tumor regression by clinical examination and compara- tive slit-lamp photography. ● RESULTS: Five consecutive patients with conjunctival melanoma (American Joint Committee on Cancer-Inter- national Union Against Cancer stages T2 [n  3] and T3 [n  2]) were included. Two patients had recurrent corneal tumors, eight and 13 months after local excision, cryotherapy, and topical mitomycin C therapy. Two months after topical interferon alfa-2b treatment, the lesions regressed without side effects. Two additional patients (who could not tolerate topical mitomycin C) were switched to topical interferon alfa-2b. They expe- rienced transient chemical conjunctivitis and have no signs of recurrence (mean, 15 months of follow-up). The fifth had recurrent tumor despite multiple surgeries. This melanoma did not respond to topical interferon alfa-2b nor did the patient tolerate treatment (keratoconjuncti- vitis). No systemic side effects were noted. ● CONCLUSIONS: We present evidence that conjunctival and corneal melanoma regresses after exposure to topical interferon alfa-2b. A larger-scale longer-term study must evaluate the long-term efficacy and safety of this therapy. (Am J Ophthalmol 2008;145:124 –129. © 2008 by Elsevier Inc. All rights reserved.) C ONJUNCTIVAL MALIGNANT MELANOMA (CMM) has been reported to exhibit a two-fold increased incidence in the United States and Finland. 1,2 These findings, along with 12% to 50% recurrence rates after treatment as well as a 26% incidence of metastasis, draws attention to the need for improved treatment options. 3 In the treatment of small or medium epibulbar tumors, local excision followed by double-freeze cryother- apy offers an 88% local control rate. 4,5 However, manage- ment of large, diffuse, and multifocal tumors is both more complex and less effective. 3 Since 1992, topical mitomycin C chemotherapy has been used alone or as adjunct treatment for conjunctival primary acquired melanosis (PAM) with atypia and CMM. 6–8 Proponents of this approach suggest it ad- dresses diffuse, multifocal disease as well as melanoma sine pigmento. 6,8 At this time, the most widely used agent is mitomycin C; however, other reported medica- tions include 5-fluorouracial, urea, thiotepa, and dini- trochlorobenzene. 9 Of interest, recent reports on topical and subconjunctival injection of interferon alfa-2b suggest its safety and efficacy against histologically proven squamous conjunctival and cor- neal intraepithelial neoplasia. 10 –13 The most common side effect is chemical conjunctivitis that resolves after therapy. In addition, resolution of conjunctival Kaposi sarcomas in HIV- positive patients with subconjunctival and topical interferon alfa-2a has been noted (Finger PT, personal observation, 2006). Last, systemic interferon alfa-2b therapy is used for treatment of metastatic cutaneous melanoma. 14 Herein, we present a retrospective case series of five patients who re- ceived topical interferon alfa-2b as treatment for histologi- cally proven CMM and PAM with atypia. METHODS THIS STUDY WAS A RETROSPECTIVE REVIEW OF FIVE CON- secutive patients with biopsy-proven CMM with PAM with atypia who had received treatment with topical interferon alfa-2b chemotherapy (see Table). According to the American Joint Committee on Cancer-International Union Against Cancer (AJCC-UICC) tumor, node, me- tastasis (TNM) classification, 13,14 three patients were T2N0M0 and two were T3N0M0. 15–17 Metastatic surveys included total body 2-deoxy-2-[18F] fluoro-D-glucose ( 18 FDG) positron emission tomography and computed tomography (PET/CT) with fusion. The initial surgical technique involved a wide surgical excision of the main nodular component of the tumor, including a 2-mm tumor-free margin with frozen and permanent section histoanalysis. Then, cryotherapy was applied with spatulated cryoprobes to the tumor margins in Accepted for publication Aug 20, 2007. From The New York Eye Cancer Center, New York, New York (P.T.F., K.J.C.); and The New York Eye and Ear Infirmary, New York, New York (P.T.F., R.W.S.). Inquiries to Paul T. Finger, The New York Eye Cancer Center, 115 East 61st Street, New York, NY 10065; e-mail: pfinger@eyecancer.com © 2008 BY ELSEVIER INC.ALL RIGHTS RESERVED. 124 0002-9394/08/$34.00 doi:10.1016/j.ajo.2007.08.027