topical therapy, although there were fewer numbers of these cells with longer durations of treatment. Dysplastic cellular changes were also seen in the normal epithelial cells, includ- ing cytoplasmic vacuolization, cytomegaly, and multiple nuclei or binucleation; these changes persisted up to 8 months after the completion of topical MMC treatment (McKelvie and Daniell 2001). Chronic histopathologic changes to the conjunctival epithelium had also been reported by Demirci and colleagues (2000) in patients treated with topical MMC. In patients who had received between 7–28 days of topical MMC, the authors showed that there was diffuse conjunctival epithelial atrophy and thinning, dyskeratosis, focal keratini- zation, and stromal ﬁbrosis in areas with atrophic epithelium. The authors noted that these conjunctival changes persisted for an extended period even after the treatment was discon- tinued, similar to the long-term effects of ionizing radiation (Demirci et al 2000; McKelvie and Daniell 2001). When prescribing topical MMC for the treatment of conjunctival neoplasms, certain precautions should be taken. Patients and their families are advised to wear latex gloves at all times when handling the medication, and pregnant women should avoid any contact with the drug. MMC is relatively unstable in solution and its action decreases in 8–10 days (Midena et al 2000). Therefore, the formulation for topical MMC needs to be refrigerated and a new bottle dispensed for each week of treatment. Since MMC is a chemotherapeutic agent, all residual bottles should be returned to the pharmacy for proper disposal. Patients should also be instructed to occlude their puncta for at least 5 minutes after the topical instillation of MMC to avoid nasopharyngeal and systemic exposure to the drug. 5-Fluorouracil Similar to MMC, topical 5-FU has also been used to inhibit the proliferation of subconjunctival ﬁbroblasts after glau- coma ﬁltration surgery (Katz et al 1995). Several reports have also conﬁrmed the clinical efﬁcacy of topical 5-FU in the treatment of preinvasive ocular surface neoplasia (Yeatts et al 1995, 2000; Midena et al 2000). 5-FU is an antime- tabolite used to treat many epithelial cancers because of its actions on rapidly proliferating cells. Within the cell, the drug inhibits thymidylate synthetase during the S phase of the cell cycle, preventing DNA and RNA synthesis in rapidly dividing cells because of a lack of thymidine. Although the 1% dose of 5-FU used in clinical studies is somewhat arbi- trarily chosen, this dosage appears to be well-tolerated in the vast majority of patients. In addition, the cytologic changes associated with MMC have not been observed with topical Clinical Ophthalmology 2008:2(3) Topical treatment options for conjunctival neoplasms 5-FU (de Keizer et al 1986; Yeatts et al 2000). Finally, 5-FU is an inexpensive drug, easily handled by medical personnel and patients, and is stable in aqueous solution for at least 3 weeks. 5-FU also does not require refrigeration, as does MMC (Midena et al 2000). Alpha-Interferon Interferons are a family of glycoprotein molecules that act at cell surface receptors to produce antiviral and antitumor activities through direct and indirect mechanisms (Baron et al 1991; Schechter et al 2002). Systemic interferon-alpha is an established therapeutic agent for hairy cell leukemia, condyloma acuminate, Kaposi’s sarcoma in AIDS, and hepatitis (both B and C). Intralesional interferon has also been reported to be effective at treating squamous and basal cell carcinomas of the skin (Fenton et al 2002). Topical IFNapha2b is the recombinant form of interferon-alpha, and this formulation has been shown to be effective for treating conjunctival and corneal intraepithelial neoplasia (CIN) (Vann and Karp 1999). The mechanism of action for treat- ing CIN may be related to an indirect antiproliferative effect of topical interferon on superﬁcial tumor cells, achieved by promoting the immune response through an activation of host cytotoxic effector cells (Baron et al 1991). Conjunctival neoplasms treated with topical agents Primary acquired melanosis and conjunctival melanoma Primary acquired melanosis is a proliferative condition of melanocytes that populate the conjunctival epithelium (Fol- berg et al 1984, 1985b). Clinically, PAM presents as a super- ﬁcial ﬂat, brown discoloration of the conjunctiva that most commonly affects middle-aged or older Caucasian patients. The margins of PAM may be indistinct and difﬁcult to iden- tify clinically, particularly if there are variably pigmented or nonpigmented areas. The extent of conjunctival involvement with PAM may also increase and decrease over time. There are two distinct histologic subtypes: PAM without atypia is characterized by benign-appearing melanocytes that populate the basilar epithelium, whereas PAM with atypia is char- acterized by cytologically abnormal melanocyte subtypes, such as polyhedral cells, spindle cells, large dendritiform cells, or epithelioid cells. The abnormal cells that character- ize PAM with atypia may remain restricted to the basilar region or spread to all level of the epithelium. PAM without atypia appears to have minimal malignant potential, whereas 505