Shields and colleagues (2002) also reported excellent clinical results in ten patients with conjunctival and corneal SCC treated with topical MMC as primary therapy. All of these patients had clinically evident tumors and complete tumor regression was documented in all ten cases; no recurrences have been observed with a mean follow-up of 22 months. In general, the stronger concentration of 0.04% MMC was used by the majority of authors for invasive SCC, with a treatment duration ranging between 3–6 weeks. OSSN and 5-FU There are a limited number of studies describing the use of 5-FU for OSSN (de Keizer et al 1986; Yeatts et al 1995; Midena et al 2000). de Keizer and collagues (1986) reported the successful treatment of two patients affected by carcinoma in situ of the conjunctiva and cornea with 1% topical 5-FU (de Keizer et al 1986). Then Yeatts and colleagues (1995) reported using 5-FU drops to treat six patients with a variety of OSSN lesion: three cases of carcinoma in situ, one case of invasive carcinoma, and two cases of intraepithelial dyspla- sia. These authors used 5-FU four times daily for 14–21 day cycles with no long-term side effects, although two of the six patients developed tumor recurrences that required surgical excision. Yeatts and colleagues (2000) later published a series of 7 patients with CIN lesions with a minimum of 7 months follow-up. In this study, pulsed dosing of 1% 5-FU was used, with durations of 2–4 days for each cycle. The number of initial treatment cycles was two to six, with the time between cycles being 30–45 days. Three patients in this series experienced tumor recurrence; two patients were successfully treated with additional cycles of topical 5-FU and one patient required treatment with topical MMC for persistent disease. Finally, Midena and colleagues (2000) reported the results of a prospective, nonrandomized study to evaluate the efﬁcacy of topical 5-ﬂuorouracil (5-FU) in the treatment of recurrent, partially excised, and selected untreated conjunctival SCC. This study had a standardized protocol for following patients and the clinical results were not inﬂuenced by concomitant surgery or other treatments. All of the patients in this study had invasive SCC, and they were treated daily for a course of 4 weeks with topical 1% 5-FU. Cytologic smears were performed at 1, 3, and 6 months. At the last follow-up examination, a conjunctival biopsy was performed at the site of the original lesion, except for two patients who refused any surgery. Patients in the study had a minimum follow up of 13 months, with a range of 13–53 months and a mean of 27 months. Seven patients had com- plete and stable regression of their conjunctival lesions. One Clinical Ophthalmology 2008:2(3) Topical treatment options for conjunctival neoplasms patient had a clinical local recurrence, six months after topical chemotherapy. He was successfully retreated with a second 4 week course of topical 5-FU. Overall, no malignant cells were found after the 4 week course of treatment, except for the recurrent case, on examination of conjunctival cytological smears. In all cases, post-treatment biopsies conﬁrmed the accuracy of these cytological results. In summary, all eight cases with SCC were treated with topical 5-FU alone with remission of the disease after one or more courses of local chemotherapy. Despite the signiﬁcant recurrence rate observed in the earlier studies with 5-FU, the Midena paper demonstrated that topical chemotherapy with 5-FU alone was effective in eradicating SCC in these patients without major and/or long term side effects. Although it is difﬁcult to make conclusions based on one report, this pilot study was well-designed and clinicians should be encouraged about the prospect of curing invasive SCC lesions with a 4 week course of topical 5-FU. In addition, 5-FU may have a more favorable side effect proﬁle than topical MMC, although more studies are needed to validate this potential advantage. OSSN and alpha-interferon Between 1993 and 1999, there were encouraging case reports of patients with conjunctival and corneal CIN being treated successfully with interferon (Maskin 1994; Vann and Karp 1999; Schechter et al 2002). Topical interferons for OSSN were ﬁrst reported to be efﬁcacious in a case reported by Maskin (1994). A subsequent paper by Vann and Karp (1999) described the successful use of a combination of intralesional and topical interferon in six patients with biopsy-proven primary or recurrent CIN. Although the follow-up in these early case reports was only 9–19 months, complete resolu- tion of these lesions was noted, and patients were able to tolerate topical interferon therapy for 2–5 months. Karp and colleagues (2001) have also published a case series of 5 patients treated with topical interferon for corneal and con- junctival intraepithelial neoplasia, 2 of whom were treated for recurrent disease. One patient received almost 4 months of continuous therapy (17 weeks), with clinical resolution noted at 13 weeks. The only patient who experienced a recur- rence in this series was treated successfully with a second course of topical interferon which lasted 2 months, and this was followed by another 8 months of maintenance therapy. Boehm and Huang (2004) reported using topical interferon as a single therapeutic agent in the treatment of recurrent corneal and conjunctival intraepithelial neoplasia. All seven patients in this series had suffered recurrences after surgical 511