Kim and Abramson topical MMC can be considered a viable therapeutic option for patients with diffuse PAM with atypia diagnosed on incisional biopsy or those patients with positive margins or residual areas of pigment following local excision. In most protocols, MMC 0.04% has been used 4 times daily for 2 week cycles, with breaks of 1–2 weeks between cycles, and a total of 2–4 cycles to allow for a complete clinical response. It should be emphasized that not all of the areas of pigmentation resolve completely, and a clinical response may continue to be observed for months after the topical treatment has been stopped. Pigment that does not resolve completely after topical MMC therapy should not be considered a treat- ment failure, since this may represent a grouping of normal melanocytes with increased pigmentation or perhaps extra- cellular pigment (Pe’er and Frucht-Pery 2005). If a patient has completed an adequate course of therapy but there are residual areas of pigmentation, the lesion should be observed at regular intervals for evidence of progression or re-biopsied. If the area of pigment progresses during the period of follow- up or the biopsy shows persistent disease, then patients can have a re-treatment with topical MMC if the area is diffuse or local excision if the area is fairly circumscribed. For invasive conjunctival melanoma, the role of topical MMC in the treatment algorithm is not well-established. Among the 16 patients that have been treated with topical MMC as either primary or adjuvant therapy, 5 cases experi- enced tumor recurrences (37.5%) and 3 patients eventually required orbital exenteration for local tumor control. It was noted by Demirci and colleagues (2000) that nodular nests of subepithelial melanoma appeared resistant to topical MMC. Pe’er and Frucht-Pery (2005) successfully treated 3 patients with conjunctival melanoma using topical MMC as primary therapy, although these three patients had only microscopic invasion on histopathology and one of the patients devel- oped a tumor recurrence. Topical MMC was also used as an adjuvant agent after surgical excision by Finger’s group in 6 patients with conjunctival melanomas, and 3 of these patients experienced tumor recurrences. Although the short course of topical therapy in these patients was well-tolerated, the ben- eﬁcial effect of adjuvant MMC for conjunctival melanomas is questionable (Werschnik and Lommatzsch 2002). Based on the studies that have been published to date, caution is warranted when treating any patient with an invasive con- junctival melanoma with topical MMC as primary treatment. If a conjunctival melanoma is surgically excised and the surgical margins demonstrate an area of PAM with atypia or residual superﬁcial disease of the cornea, topical therapy can be considered a viable alternative to repeat surgical excision. 508 If the surgical margin is positive for invasive melanoma, surgical excision of the involved area should be strongly considered. This recommendation is particularly relevant for patients with high risk features for metastatic disease, such as location in the caruncle or palpebral conjunctiva, thickness greater than 0.8 mm, previous history of tumor recurrence, or pagetoid growth pattern. Ocular surface squamous neoplasia Lee and Hirst (1995) ﬁrst proposed the term OSSN to encompass the entire spectrum of dysplastic and carcinomatous lesions of the ocular surface. In its current usage, the term OSSN represents a spectrum of disorders from simple dysplasia to carcinoma in situ to invasive squamous cell carcinoma involving the conjunctiva, limbus, and/or cornea. OSSN lesions involving only the epithelium can also be termed conjunctival or CIN (Pizzarello and Jakobiec 1978). Similar to other mucosal sites, CIN can be classiﬁed as mild, moder- ate, and severe dysplasia based on the extent of involvement; lesions that involve the basal one-third of the conjunctiva are classiﬁed as mild, those involving the inner two-thirds are classiﬁed as moderate, and lesions that are full thickness are termed severe dysplasia or carcinoma in situ. Invasive disease is most commonly classiﬁed as squamous cell car- cinoma of the conjunctiva, although more rare variants such as mucoepidermoid and spindle cell carcinoma can be seen (Lee and Hirst 1995). The most common clinical presentation for OSSN is an elevated, vascularized lesion in the limbal region of older male patients who have a history of signiﬁcant exposure to ultraviolet radiation. Pizzarello and Jokobiec (1978) have described the macroscopic appearance of OSSN as being gelatinous, velvety, papilliform, or leukoplakic. Two other appearances, nodular and diffuse, have also been described (Blodi 1973). Occasionally, OSSN is diagnosed in younger patients with predisposing conditions, such as the human immunodeﬁciency virus or xeroderma pigmentosum. Human papilloma virus (HPV) is also thought to play a role in the development of OSSN, perhaps in combination with other risk factors such as UV-B exposure. Investigators have detected evidence of active HPV infection by polymerase chain reaction in CIN lesions (Karcioglu and Issa 1997; Scott et al 2002), although it is clear that not all patients infected with HPV develop CIN. Wide surgical excision has been considered the treatment of choice for OSSN lesions and specialized techniques for decreasing recurrence rates have been described (Shields et al 1997). Despite adjunctive cryotherapy, intraoperative application of alcohol, and other precautions, recurrence rates Clinical Ophthalmology 2008:2(3)