Complete Resolution of Bilateral Choroidal Metastases of Cutaneous Melanoma With Combined Targeted Therapy.

Ocular metastasis is the most common intraocular malignancy.[1,2] Cutaneous melanoma accounts for 2% of ocular metastatic disease[1,2]; they tend to be bilateral, large, flat, and multifocal.[2] The 5-year survival rate for cutaneous melanoma metastatic to the eye was 33% in a large cohort analysis.[2]

A 67-year-old man was referred for bilateral mild blurry vision and floaters. His medical history was significant for metastatic cutaneous melanoma with BRAF (B-Raf proto-oncogene) V600K mutation. Ophthalmologic examination showed multiple, diffuse, nonelevated, pigmented choroidal lesions in both eyes (Figure 1, A and B). Fluorescein angiography demonstrated blockage and lack of intrinsic tumor vascularity. Optical coherence tomography showed normal overlying internal retinal layers and pigment epithelium structure without exudative or degenerative changes and minimal thickening of the choroid. Severe progression of his metastatic disease was documented with increased number and size of cutaneous, subcutaneous lesions, new-onset liver and uveal metastases when receiving systemic and intralesional immunotherapy. The patient was started on combined BRAF/MEK (Mitogen-activated protein kinase/Extracellular signal-regulated Kinase) (dabrafenib/trametinib) inhibitor treatment. After 18 months of combined targeted therapy, the choroidal lesions showed complete regression in both eyes (Figure 1, C and D) along with stable systemic disease. No ocular side effects were experienced during targeted therapy and no recurrence of choroidal lesions was documented during a 9-month follow-up. Based on a systematic literature review (PubMed and Google Scholar), this seems to be the first documented case of regression of uveal metastasis with combined targeted therapy.

Fig. 1.

Diffuse, multifocal, pigmented choroidal metastases in the right (A) and left eye (B) of a patient with cutaneous melanoma. Complete regression of uveal metastases in response to combined BRAF/MEK inhibitor therapy (right eye, C; left eye, D).

Treatment of uveal metastasis may be required if the metastatic lesion seems chemotherapy-resistant and vision or globe-threatening.[1] Shields et al reported spontaneous regression of uveal metastasis of cutaneous melanoma[3] and others found resolved choroidal metastatic lesions from melanoma in response to chemotherapy (carmustin, cisplatin).[4,5] Our case indicated that combined BRAF and MEK inhibition may provide a benefit in the treatment of uveal metastasis from cutaneous melanoma.