For many years, management of posterior uveal melanomas was controversial for 2 reasons: (1) data on the natural history of untreated patients with posterior uveal melanoma were limited; and (2) there were insufficient data on patients who were matched for known and unknown risk factors and managed by different therapeutic techniques to compare their effectiveness. Currently, both surgical and radiotherapeutic techniques are used to treat posterior uveal melanoma. The choice of treatment depends on 4 factors:
size, location, and extent of the tumor
vision status of the affected eye and of the fellow eye
age and general health of the patient
patient and physician preference
Significant controversy persists regarding the diagnosis and management of small choroidal melanomas. Treatment should be considered for lesions with any of the 5 main risk factors for growth (thickness greater than 2 mm, subretinal fluid, symptoms, lipofuscin, or tumor margin touching the optic nerve head) and all lesions with documented growth. Short-term observation to verify growth of a suspected small uveal melanoma has traditionally been considered appropriate, especially when the tumor is located in the macular area. As mentioned earlier, FNAB can be an alternative but is technically challenging for small tumors and carries risks to vision. Observation of active and larger melanomas may be appropriate in very el derly patients and those with systemic illness who are poor candidates for any therapeutic intervention.
Historically, enucleation has been the gold standard in the treatment of malignant intraocular tumors. A past hypothesis that surgical manipulation of eyes containing a melanoma would lead to tumor dissemination and increased mortality is no longer accepted. Enucleation remains appropriate for some small to medium (T1 and T2) and many large (T3) and very large (T4) choroidal melanomas, especially when useful vision has been lost or when the patient declines other treatments. The COMS found no evidence that pre-enucleation external beam radiotherapy performed on patients with large choroidal melanomas improved 5-year survival. However, local orbital recurrence was more frequent after enucleation alone.
Brachytherapy with a radioactive plaque
The application of a radioactive plaque to the sclera overlying an intraocular tumor is the most common globe-sparing method to treat uveal melanoma. With this technique, which has been widely available since the 1950s, a very high dose of radiation can be delivered to the tumor (typically 80–100 gray [Gy] to the tumor apex and up to 1000 Gy to the tumor base), while a comparatively lower dose is delivered to the surrounding normal structures of the eye. Although various isotopes can be used (eg, cobalt 60, strontium 90, iridium 192, and palladium 103), the most common are iodine 125 (γ-rays) and ruthenium 106 (β-rays). In the United States, iodine 125 is the most frequently used isotope in the treatment of uveal melanomas of any size, whereas in Eu rope, ruthenium 106 is preferred for smaller melanomas. Advances in intraoperative localization, especially the use of ultrasonography (see Fig 17-10B), have increased local tumor control rates, which typically are greater than 90%. In most patients, the tumor decreases in size (Fig 17-13); in others, the result could be total flattening of the tumor or little change in size, although clinical and ultrasonographic changes may be evident. Though rare, local recurrence may occur; therefore, monitoring of treatment response with serial imaging, including photography and ultrasonography, is important. Regrowth may occur at the tumor margin or more diffusely.
American Brachytherapy Society–Ophthalmic Oncology Task Force. The American Brachytherapy Society consensus guidelines for plaque brachytherapy of uveal melanoma and retinoblastoma. Brachytherapy. 2014;13(1):1–14.
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.
High–linear energy transfer radiation with charged particles (protons or helium ions) is effective in managing ciliary body and choroidal melanomas, with local tumor control rates of up to 98% reported. The tumor response is similar to that observed after brachytherapy. In this technique, tantalum clips are surgically attached to the scleral surface before the first radiation fraction is delivered in order to allow localization of the tumor with MRI and CT guidance. The charged-particle beams deliver a more homogeneous dose of radiation energy to a tumor than a radioactive plaque would, and the lateral spread of radiation energy is less extensive. A specific charged-particle accelerator is required for this type of therapy and is not available in every treatment center.
Figure 17-13 Choroidal melanoma, treated. A, Mildly elevated remnant of a melanoma surrounded by atrophic chorioretinal scarring nasal to the optic nerve head after plaque brachytherapy. B, After transscleral resection of a choroidal melanoma located temporal to the macula, the RPE and choroid are absent (and the outer retina is likely atrophic), but the inner retina is present, as evidenced by its blood vessels.
(Part A courtesy of Jacob Pe’er, MD; part B courtesy of Tero Kivelä, MD.)
Depending on tumor size and location, after treatment with either plaque brachytherapy or charged-particle radiation, more than 50% of patients experience radiation-related adverse effects that limit vision, especially optic neuropathy and maculopathy. These effects are often related to radiation-induced damage to the microvasculature. They may or may not respond to intravitreal anti–vascular endothelial growth factor (anti-VEGF) treatment; however, a trial of anti-VEGF is typically offered to patients. Future studies are needed to determine optimal patient selection and treatment interval for anti-VEGF therapy. After initial radiotherapy, large tumors may cause a chronic exudative retinal detachment or may become “toxic,” often leading to neovascular glaucoma (NVG). Postradiation NVG may also occur in the absence of exudative retinal detachment. Although NVG may be treatable with conservative therapies, eyes with NVG will sometimes be secondarily enucleated. Chronic dry eye may develop with either form of radiation. Chargedparticle radiation may also be associated with cicatricial changes to the eyelid margins. When the tumor is anteriorly located, radiation cataract is common and can be managed with routine cataract extraction. These complications appear to be dose dependent and typically develop after a delay of 1 to several years.
External beam radiotherapy
Conventional external beam radiotherapy is ineffective for uveal melanoma. In recent years, some centers have used fractionated stereotactic radiotherapy and gamma knife radiosurgery as the primary treatment. Further study of these methods is warranted, but the published results and adverse effects are comparable to those of other irradiation methods.
Transpupillary thermotherapy and photodynamic therapy In the past, laser photocoagulation played a limited role in the treatment of melanocytic tumors. Today, transpupillary thermotherapy (TTT), in which a long-duration, large-spot-size, relatively low-energy infrared diode laser raises the temperature of the choroid, is used to manage selected small choroidal melanomas and, more frequently, to augment plaque brachytherapy or to control a local recurrence at the tumor margin. Studies suggest that TTT alone is associated with a higher rate of local tumor recurrence than is brachytherapy. Some of these recurrences are extraocular.
Surgical excision Surgical transscleral resection or endoresection during vitrectomy has been successfully performed in eyes with malignant and benign intraocular tumors (see Fig 17-13B). Concerns regarding surgical excision include the inability to evaluate tumor margins for residual disease, the high incidence of pathologically recognized scleral and retinal involvement in medium and large choroidal melanomas, and the possibility of spreading the tumor intraocularly and extraocularly. The surgical techniques are generally quite demanding, requiring an experienced surgeon with specialized training. Today, local excision of a uveal melanoma is coupled with adjuvant radiotherapy, such as brachytherapy or proton beam therapy, to reduce local recurrence rates to levels comparable to those after radiotherapy.
Chemotherapy Currently, chemotherapy is not effective in the treatment of primary uveal melanoma, nor is it routinely used in the treatment of metastatic disease.
Immunotherapy In immunotherapy, systemic cytokines, immunomodulatory agents, or vaccine therapy is used to try activating a tumor-directed T-cell immune response. This treatment is theoretically 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 is not available for primary uveal melanoma. Immunotherapy for metastatic disease has been used with limited success.
Exenteration Traditionally advocated for patients with extrascleral extension of a posterior uveal melanoma, exenteration is rarely used today. Unless orbital invasion is very advanced, the current trend is toward more conservative treatment for these patients, with either enucleation plus a limited tenonectomy or modified plaque brachytherapy or proton beam therapy.
Excerpted from BCSC 2020-2021 series: Section 4 - Ophthalmic Pathology and Intraocular Tumors. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.