compared with brachytherapy.

Cryotherapy Although cryotherapy using a triple freeze-thaw technique has been tried in the treatment of small choroidal melanomas, it is not considered standard therapy and is not currently undergoing further evaluation for efficacy.

Transscleral diathermy Diathermy is contraindicated in the treatment of malignant intraocular tumors because the induced scleral damage may provide a route for extrascleral extension of tumor cells.

Surgical excision of tumor Surgical excision has been performed successfully in many eyes with malignant and benign intraocular tumors. Concerns regarding surgical excision include the inability to evaluate tumor margins for residual disease and the high incidence of pathologically recognized scleral, retinal, and vitreous involvement in medium and large choroidal melanomas. When this treatment is used, the surgical techniques are generally quite difficult, requiring an experienced surgeon. In some centers, local excision of uveal melanoma has been coupled with globe-conserving radiotherapy, such as brachytherapy.

Chemotherapy Currently, chemotherapy is not effective in the treatment of primary or metastatic uveal melanoma. Various regimens have been used, however, for palliative treatment of patients with metastatic disease.

Immunotherapy Immunotherapy uses systemic cytokines, immunomodulatory agents, or local vaccine therapy to try to activate a tumor-directed T-cell immune response. This treatment may be appropriate for uveal melanoma, because primary tumors arise in an immune-privileged organ and may express antigens to which the host is not sensitized. Currently, however, immunotherapy for primary uveal melanoma is not available, and immunotherapy for metastatic disease is still under investigation.

Exenteration Exenteration, traditionally advocated for patients with extrascleral extension of a posterior uveal melanoma, is rarely employed today. The current trend is toward more conservative treatment for these patients, with enucleation plus a limited tenonectomy. The addition of local radiotherapy appears to achieve survival outcomes similar to those of exenteration.

Bergman L, Nilsson B, Lundell G, Lundell M, Seregard S. Ruthenium brachytherapy for uveal melanoma, 1979–2003: survival and functional outcomes in the Swedish population. Ophthalmology. 2005;112(5):834–840.

Damato B, Jones AG. Uveal melanoma: resection techniques. Ophthalmol Clin North Am. 2005;18(1):119–128.

Diener-West M, Earle JD, Fine SL, et al. The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma, III: initial mortality findings. COMS report no. 18. Arch Ophthalmol. 2001;119(7):969–982.

Hawkins BS; Collaborative Ocular Melanoma Study Group. The Collaborative Ocular Melanoma Study (COMS) randomized trial of pre-enucleation radiation of large choroidal melanoma: IV. Ten-year mortality findings and prognostic factors. COMS report no. 24. Am J Ophthalmol. 2004;138(6):936–951.

Prognosis and Prognostic Factors

According to an analysis of 5403 patients with a choroidal and ciliary body melanoma of known tumor size, ciliary body involvement, and extraocular extension, 10-year survival estimates for AJCC stages I, IIA to IIB, and IIIA to IIIC were 88%, 80%, 67%, 45%, 27%, 10%, respectively (see the AJCC staging forms in the appendix). Retrospective analysis of patients with melanoma suggests that clinical risk factors for mortality are

larger tumor size at time of treatment

tumor growth

anterior tumor location (eg, ciliary body) extraocular extension

older age

tumor regrowth after globe-conserving therapy

rapid decrease in tumor size after globe-conserving therapy juxtapapillary tumors

Histologic and molecular features associated with a higher rate of metastases include

epithelioid cells

high mitotic index and high cell proliferation indices

extracellular matrix patterns (loops, networks of loops, and parallel with cross-linking) mean diameter of the 10 largest nucleoli

tumor-infiltrating lymphocytes monosomy 3, trisomy 8

BAP1 mutation, wild type E1F1AX and SF3B1 gene expression profiling (class 1B and class 2)

A more in-depth discussion is provided in Chapter 12.

Harbour JW, Chao DL. A molecular revolution in uveal melanoma: implications for patient care and targeted therapy. Ophthalmology. 2014;121(6):1281–1288.

Kujala E, Damato B, Coupland SE, et al. Staging of ciliary body and choroidal melanomas based on anatomic extent. J Clin Oncol. 2013;31(22):2825–2831.

Sisley K, Rennie IG, Parsons MA, et al. Abnormalities of chromosomes 3 and 8 in posterior uveal melanoma correlate with prognosis. Genes Chromosomes Cancer. 1997;19(1):22–28.

Collaborative Ocular Melanoma Study (COMS)

Survival data from the COMS have been reported for the randomized clinical trials of large and medium choroidal melanoma and for the observational study of small choroidal melanoma. These results provide the framework for patient discussions concerning treatment-related long-term survival, rates of globe conservation with 125I brachytherapy, and predictors of small-tumor growth.

COMS Large Choroidal Melanoma Trial

evaluated 1003 patients with choroidal melanomas greater than 16 mm in basal diameter and/or greater than 10 mm in apical height

compared enucleation alone with enucleation preceded by external-beam radiotherapy reported no statistically significant difference in 5-year and 10-year survival rates between cohorts (approximately 60% and 40%, respectively)

concluded that adjunctive radiotherapy did not improve overall survival

established the appropriateness of primary enucleation alone in managing large choroidal melanomas that are not amenable to globe-conserving therapy

COMS Medium Choroidal Melanoma Trial

evaluated 1317 patients with choroidal melanomas ranging in size from 6 mm to 16 mm in basal diameter and/or 2.5 mm to 10 mm in apical height

compared standardized enucleation and 125I brachytherapy

all-cause mortality at 5 years and 10 years: no significant difference between cohorts