Abstract and Introduction
Abstract
Choroidal melanoma is the most common primary intraocular malignancy in adults. Alternative treatment modalities have been proposed in recent years including enucleation, local resection, plaque brachytherapy, charged-particle radiotherapy, stereotactic photon beam irradiation therapy, transpupillary thermotherapy and photodynamic therapy. This review aims to focus on all the available therapeutic options in choroidal melanoma and update the reader on the current status of each modality. Treatment of choroidal melanomas should be directed towards reducing the risk of recurrences, as it is known that recurrent tumors are associated with an increased rate of metastatic disease and poor prognosis. Advances in genetics and cytogenetics can enhance the accuracy of patient prognostication.
Introduction
Uveal melanoma is the most common primary intraocular malignant tumor in adults. There are several studies published on the incidence of uveal melanoma, regarding the variable rates in both the USA and Europe. The mean age-adjusted incidence of uveal melanoma in the USA is reported to be 5.1 per million people annually. Although the difference between various ethnic groups has been known for many years, population-based studies on incidence of uveal melanoma in these groups are scarce. One of the few population-based studies that is present in the literature indicates that the annual age-adjusted incidence of uveal melanoma was 0.31 (per million population) in black, 0.38 in Asian and 1.67 in Hispanic populations. The two main objectives of treating the tumor are to reduce the risk of metastatic spread and to salvage the eye with useful vision whenever feasible. The selection of appropriate treatment largely depends on the size and location of the tumor; associated ocular findings; the status of the fellow eye; and individual factors, including age, life expectancy, quality of life issues, concurrent systemic diseases and patient expectations. In addition, recent cytogenetic findings suggest that even small melanomas with complete monosomy 3 have poor prognosis which would necessitate prompt early treatment. This review aims to focus on all of the available therapeutic options for choroidal melanoma and update the reader on the current status of each modality.
Choroidal melanomas are classified as either small (<10 mm in diameter and <3 mm in height), medium (10–15 mm in diameter and 3–5 mm in height) or large (>15 mm in diameter and >5 mm in height). The TNM (tumor, lymph node and metastasis) staging of uveal melanoma, which is improved and currently being used, categorizes tumors according to their size, ciliary body involvement and extraocular spread. The diagnosis and then the implementation of appropriate treatment are straightforward in the majority of choroidal melanomas. However, small melanomas, which sometimes cannot easily be differentiated from nevi, continue to generate debate. Until recently, these small melanocytic lesions were usually observed if they remained stable without documented growth. Advances in cytopathology, the demonstration of monosomy 3 in highly aggressive and rapidly progressive tumors that metastasize, and classification of uveal melanomas based on gene-expression profiles had a major impact on the management of small melanocytic tumors. It is now known that micrometastases may occur several years before the diagnosis of a choroidal melanoma and that metastases may already start when the tumor diameter is 3 mm and the thickness is only 1.5 mm. Identifying the small melanoma is therefore vital and observation of the following features are strongly in favor of a malignant tumor rather than a nevus: thickness >2 mm (an arbitrary cutoff value), asymmetric growth, documented increase of 0.3 mm in thickness and 0.5 mm in basal diameter, presence of subretinal fluid, visual symptoms, orange pigment, tumor margin within 3 mm from the optic disc, acoustic hollowness on ultrasonography, absence of halo around the tumor, absence of drusen over the lesion, and looping vessels on indocyanine green angiography. There is a point worth remembering: although growth of choroidal melanocytic lesions has generally been regarded as an indicator of malignancy, enlargement of small choroidal nevi without evidence of malignant transformation has been documented, especially in younger patients.
Current treatment options of choroidal melanoma include enucleation, plaque brachytherapy, proton beam radiotherapy, stereotactic photon beam irradiation, local resection, photodynamic therapy (PDT) and transpupillary thermotherapy as an adjunct treatment.