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Dramatic regression of conjunctival and corneal acquired melanosis with topical mitomycin C
  1. Carol L Shields,
  2. Hakan Demirci,
  3. Jerry A Shields,
  4. Christopher Spanich
  1. Ocular Oncology Service, Wills Eye Hospital Service, Thomas Jefferson University, Philadelphia, PA, USA
  1. Correspondence to: Carol L Shields, MD, Ocular Oncology Service, Wills Eye Hospital, 900 Walnut Street, Philadelphia, PA 19107, USA

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Conjunctival primary acquired melanosis is the most important precursor of conjunctival malignant melanoma.1,2 Primary acquired melanosis appears as flat, patchy, non-cystic pigmentation in the conjunctival epithelium and can remain dormant for years or show slow progression.2 Studies have shown that it leads to conjunctival melanoma in approximately 1% to 30% patients.3,4 Treatment of primary acquired melanosis includes observation, excisional biopsy, alcohol epitheliectomy, cryotherapy, and topical chemotherapy.1,2,5,6 We illustrate a dramatic case where topical chemotherapy provided complete regression of advanced, aggressive primary acquired melanosis.

A 73 year old white man had noted slowly progressive pigmentation on the surface of his right eye for 5 years. A biopsy revealed intraepithelial conjunctival melanosis with atypia. The patient was referred to the Oncology Service at Wills Eye Hospital for evaluation and management. On examination, his visual acuity was 20/20 right eye and 20/40 left eye. Intraocular pressures were 13 mm Hg in both eyes. The interior of both eyes was unremarkable with mild nuclear sclerosis and mild retinal pigment epithelial mottling. The only abnormality on examination was the presence of patchy, flat, brown conjunctival pigmentation on the right eye for 360 degrees on the bulbar and forniceal conjunctiva with involvement of the caruncle, upper tarsal conjunctiva, and entire surface of the cornea (Fig 1). There was no thickening or excessive vascularity to suggest malignant melanoma.

One option for management of this precancerous condition was extensive conjunctival excision and 360 degrees of cryotherapy followed by complete alcohol induced corneal epitheliectomy with anticipation of extensive postoperative scarring, possible symblepharon, and likely conjunctival overgrowth onto the cornea because of the absence of corneal stem cells. The other options included topical chemotherapy with mitomycin C or low dose radiotherapy with a custom designed conformal plaque. Mitomycin C was selected and the patient was treated with a total of 6 weekly cycles of topical mitomycin C 0.04% four times daily interrupted by a week's hiatus of no medication between each cycle.

Three months after therapy, the primary acquired melanosis was 80% resolved and at 10 months' follow up, the melanosis had nearly completely disappeared with minor granular pigment near the limbus (Fig 2) During the weeks of topical chemotherapy, the patient had occasional symptoms of ocular irritation and periocular cutaneous erythema and minor oedema. The ocular surface was injected during treatment but, on follow up, there was no chronic ocular surface disease or skin or cilia abnormality.

Topical mitomycin C ophthalmic preparation has been found to be safe and effective for conjunctival squamous neoplasia.7 Its usefulness for conjunctival melanocytic neoplasia is debatable and not yet proved in a large series of patients. A recent study on a small number of patients with conjunctival melanoma and melanosis indicated a possible role for topical chemotherapy, but the authors advised further investigation.6 In this regard, we prefer to reserve mitomycin C therapy for patients with biopsy proved primary acquired melanosis with atypia. An important observation in our case was the effectiveness of topical chemotherapy for corneal melanosis where other methods of treatment could have led to scarring, conjunctival overgrowth, and ultimate visual loss. We emphasise, however, that patients should be monitored biomicroscopically while taking the medication as overuse could lead to lasting corneal and scleral tissue damage. The recommended duration of treatment has not yet been established in a randomised study. We prefer to limit treatment to two to four cycles with a non-treatment weekly hiatus between cycles to avoid complications. In summary, we report a dramatic case that supports the value of topical mitomycin C for primary acquired melanosis.

Figure 1

Before mitomycin C treatment. (A) The entire medial and lateral bulbar conjunctiva, limbus, and cornea are superficially infiltrated with brown pigment of primary acquired melanosis. A biopsy had been previously taken at the medial limbus where the pigment is absent. (B) Extensive primary acquired melanosis of superior conjunctiva with diffuse limbal and corneal pigmentation is shown. (C) Diffuse conjunctival melanosis inferiorly is demonstrated.

Figure 2

Ten months after mitomycin C treatment. (A) The corneal and conjunctival melanosis has completely resolved with minor granular pigment at the superotemporal limbus. (B) Dramatic resolution of superior melanosis with no epithelial abnormality. (C) Impressive resolution of inferior melanosis.


Support provided by the Eye Tumor Research Foundation, Philadelphia, PA (CS) and the Paul Kayser International Award of Merit in Retina Research, Houston TX (JS).