(Pe’er and Frucht-Pery 2005). MMC was used as primary treatment in all 12 cases and the duration of therapy ranged from 2–5 cycles. In four patients the pigmentation completely disappeared with MMC treatment. In the other eight patients, some remnants of pigmentation remained, and one of the patients with early invasive melanoma was noted to have a tumor recurrence during the follow-up period and was treated successfully with two more courses of MMC. This series had no patients that required surgical intervention, although the follow-up was shorter than the Kurli series (24 months vs. 81 months) (Kurli and Finger 2005). Although numerous papers have been published on the use of topical MMC for melanocytic lesions, the total number of patients identiﬁed in this review was only 38 (6 studies) (Table 1). As seen in Table 1, MMC 0.04% was the most commonly used concentration, although 0.02% was used in one case by Yuen and colleagues (2003), and one case described by Frucht-Pery and Pe’er (1996) was treated with a concentration as high as 0.4 mg/ml. The most commonly used cycle duration was 14 days, with a period of 1–2 weeks between cycles; the total course of treatment was 2–3 cycles in most series. Overall, the clinical response rate appeared to be high, although a successful treatment outcome was deﬁned somewhat differently among clinicians. Some authors deﬁned a successful clinical response as the complete disappearance of pigment and/or negative biopsies after a course of topical treatment. Other authors deﬁned clinical success as either stability of the areas of pigmentation or lack of progression of superﬁcial disease to invasive melanoma. For the purposes of our review, treatment failure was deﬁned as the develop- ment of a recurrence, either a new tumor foci or progression of the areas of pigmentation during the period of follow-up. For the group of patients with PAM without atypia treated Topical treatment options for conjunctival neoplasms with topical MMC (as primary treatment), tumor recurrence was noted in 3 out of 22 eyes, for a treatment failure rate of 13.6%. However, note that all 3 cases of PAM recurrence were seen in the study with the longest follow-up (Kurli and Finger 2005), being diagnosed 23, 43, and 54 months after the completion of topical treatment. No patient with PAM with atypia treated with topical MMC was noted to progress to invasive melanoma during the period of follow-up, and none of the patients developed regional or systemic metastasis. When considering conjunctival melanoma, some authors made a distinction between lesions with microscopic inva- sion of the basement membrane and those with invasive nests of nodular melanoma. For the purposes of our review, we grouped these lesions together since any lesion with an area of invasion through the basement membrane is considered a malignancy. For invasive melanoma, Table 1 shows that 6 out of 16 cases were diagnosed with tumor recurrences, for a failure rate of 37.5%. Although one case was treated with additional topical therapy, the other 5 cases were treated with surgical excision and even exenteration in an attempt to obtain local tumor control. Metastasis was reported in one patient with malignant melanoma who received MMC as primary therapy (Kurli and Finger 2005). Summary of MMC for melanocytic lesions The interpretation of clinical studies on topical MMC is made difﬁcult by the small sample size and variation between the studies in tumor characteristics, previous treatment, length of follow-up, dosing regimen, and whether topical MMC was used as sole therapy, adjuvant, or intraoperative therapy. For PAM with atypia, the success rate of topical MMC compares favorably with the recurrence rate that has been reported following local excision and cryotherapy. Therefore, Frucht-Pery and Pe’er 1996 Kemp et al 2002 Yuen et al 2003 Rodriguez et al 2003 Kurli and Finger 2004 Pe’er and Frucht-Pery 2005 Totals Rodriguez et al 2003 Kurli and Finger 2004 Pe’er and Frucht-Pery 2005 Totals PWA PWA PWA PWA PWA PWA PWA MM MM MM MM Table 1 Summary of clinical studies of topical MMC used as primary therapy for melanocytic lesions Author DX No. eyes Recurred Surgery Follow-up (months) 8 9–16 26 36 13–144 6–108 1 2 1 1 8 9 22 1 8 3 12 0 0 0 0 3 0 3 0 5 1 6 0 0 0 0 3 0 3 0 5 0 5 36 13–144 6–108 Abbreviations: DX, clinical diagnosis; PWA, primary aquired melanosis with atypia; MM, malignant melanoma; QID, 4x per day. Clinical Ophthalmology 2008:2(3) MMC dose (mg/ml) 0.2%–0.4% 0.04% 0.02%–0.04% 0.04% 0.04% 0.04% 0.04% 0.04% 0.04% MMC regimen (QID/weeks) 4 4 16 4 2–4 4–10 4 1–4 4–10 507