Intravitreal Melphalan for Treatment of Vitreous Seeding From Choroidal Melanoma

Abstract

Purpose: To report treatment of vitreous seeding of choroidal melanoma with monthly injections of intravitreal melphalan. Methods: Case report. Results: A 70-year-old white woman noted floaters in her left eye, and further examination revealed visual acuity of 20/30 in both eyes. Funduscopically, there was a mushroom-shaped choroidal melanoma in her left eye, measuring 9 mm in basal dimension and 4.8 mm in thickness. Notably, there was apical retinal invasion of melanoma with mild vitreous hemorrhage, without vitreous seeding. The tumor was treated with iodine-125 plaque radiotherapy using an apex dose of 70 Gy over 99 hours, designed to include the retinal invasion. The melanoma demonstrated complete regression into a nearly flat scar of 1 mm and remained stable over 4 years. Five years after radiotherapy, there were diffuse vitreous pigmented seeds of presumed melanoma origin, emanating from the site of retinal necrosis. This progressively worsened over the following 18 months, suspicious for viable melanoma cells, as visual acuity concurrently declined to 20/100. Treatment with intravitreal melphalan (10 μg/0.05 mL) was delivered on a monthly basis for 12 cycles, resulting in vitreous seeds regression, and preservation of the eye. Final visual acuity was 20/200. There were no treatment-related complications. Conclusion: Intravitreal melphalan can be considered in cases of vitreous seeding from uveal melanoma.

Intraocular Dissemination of Uveal Melanoma Cells Following Radiotherapy: Evolving Management Over the Past Decade

“…Although uncommon, intraocular dissemination of uveal melanoma cells is well-attested in the literature both prior to treatment 6,7,9,10 and following radiotherapy. 8,11 A common feature in many reported cases is tumor rupture through Bruch’s membrane with invasion of the overlying retina, 8 which was seen in all of our cases. As such, transretinal tumor invasion into the vitreous is the presumed route of tumor progression in these cases.…”

“…A recent case report described a similar patient who did not undergo vitrectomy and required 12 monthly injections of melphalan. 11 We believe that an initial vitrectomy and thorough debulking of intraocular cells can substantially reduce the number of injections, minimize the need for melphalan, and potentially improve visual function by removing vitreous opacities. We have developed a modified vitrectomy technique for eyes harboring a uveal melanoma that is safe and effective with minimal risk of intra- or extra-ocular tumor dissemination, as described in the Methods section of this paper.…”

Intravitreous Cutaneous Metastatic Melanoma in the Era of Checkpoint Inhibition

“…17 One report describes its use in a single patient (12 injections of 10 mg/0.05 ml) for the treatment of vitreous seeding from uveal melanoma with a satisfactory outcome. 18 The premise behind this technique is to deliver a high dose of local drug while sparing the body the toxicity of systemic delivery. It borrows from isolated limb perfusion of melphalan, which was described first as a single case report by Creech et al in 1957 and now is a well-established technique for inoperable recurrent cutaneous melanoma affecting an extremity.…”

Combination intravitreous melphalan and bevacizumb for cutaneous metastatic melanoma to the vitreous and retina

“…10 , 11 Like these two approaches, intravitreous melphalan injections deliver targeted cytotoxic drug to the isolated site of intraocular disease; as has been demonstrated with uveal melanoma. 12 The dose of intravitreous melphalan was selected based on our prior work relating to severe retinopathy which can occur in retinoblastoma eyes treated with melphalan doses exceeding 30 mcg. 13 2) It is established that roughly one-third of eyes with intraocular melanoma metastasis will develop neovascularization and neovascular glaucoma, 2 which are two pathological states driven by aberrant vascular endothelial growth factor.…”