Intravitreous Cutaneous Metastatic Melanoma in the Era of Checkpoint Inhibition

Abstract

Purpose: Cutaneous melanoma metastatic to the vitreous is very rare. This study investigated the clinical findings, treatment, and outcome of patients with metastatic cutaneous melanoma to the vitreous. Most patients received checkpoint inhibition for the treatment of systemic disease, and the significance of this was explored.Design: Multicenter, retrospective cohort study.Participants: Fourteen eyes of 11 patients with metastatic cutaneous melanoma to the vitreous. Methods: Clinical records, including fundus photography and ultrasound results, were reviewed retrospectively, and relevant data were recorded for each patient eye.Main Outcome Measures: Clinical features at presentation, ophthalmic and systemic treatments, and outcomes.Results: The median age at presentation of ophthalmic disease was 66 years (range, 23e88 years), and the median follow-up from diagnosis of ophthalmic disease was 23 months. Ten of 11 patients were treated with immune checkpoint inhibition at some point in the treatment course. The median time from starting immunotherapy to ocular symptoms was 17 months (range, 4.5e38 months). Half of eyes demonstrated amelanotic vitreous debris. Five eyes demonstrated elevated intraocular pressure, and 4 eyes demonstrated a retinal detachment. Six patients showed metastatic disease in the central nervous system. Ophthalmic treatment included external beam radiation (30e40 Gy) in 6 eyes, intravitreous melphalan (10e20 mg) in 4 eyes, enucleation

Primary vitreoretinal involvement and immunopositivity for BRAFV600E help distinguish metastatic from primary intraocular melanoma: a detailed histopathologic study of metastatic cutaneous melanoma to the eye

“…47,51,53,54 Francis et al recently published a series of 14 eyes with metastatic cutaneous melanoma to the vitreous, emphasizing the vitreous as an increasingly recognized site of metastatic CM. 55 Conversely, in some older reports, choroidal involvement was thought to be more common than vitreoretinal involvement. 56 Here, 85.7% of patients presented with vitreoretinal disease, with no cases primarily involving the choroid, further supporting the newer evidence.…”

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

“… 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. This characteristic vasculopathy is perhaps related to the entry of metastatic melanoma through the retinal blood vessels.…”

“…This characteristic vasculopathy is perhaps related to the entry of metastatic melanoma through the retinal blood vessels. 2 Intravitreous anti-vascular endothelial growth factor (bevacizumab) is intended to targets this, and either prevent or reverse eyes from developing neovascularization and its sequelae. The present study does not answer whether bevacizumab is prophylactically beneficial to eyes with cutaneous melanoma metastatic to the vitreoretinal in the absence of clinical neovascularization: anti-VEGF injections may be equally beneficial if initiated only at the first detection of neovascularization.…”

“… 1 Perhaps due to longer survival, there is an increased detection of previously rare sites of metastases, including cutaneous melanoma to the brain, vitreous and retina. 2 , 3 …”

Secondary ocular malignancies: A review

“…There have been several recent reports of cutaneous melanoma metastasizing to the retina and vitreous. 3 The largest report includes 14 eyes over an 8-year-period which is notable because of the paucity of reports prior to the era of immune checkpoint inhibitors. Most of these patients presented with blurry vision and/or floaters.…”