Introduction

Even though there continue to be numerous publications on management of uveal melanoma, the subject remains controversial.^1–74 Depending on the clinical circumstances, observation, transpupillary thermotherapy, plaque radiotherapy, charged particle irradiation, local resection, enucleation, orbital exenteration, chemotherapy, and immunotherapy are still being employed.¹ There has been a trend away from laser photocoagulation alone with continued interest in transpupillary thermotherapy alone, or as supplemental treatment to radiotherapy for medium-sized and some large melanomas. The recently recognized clinical risk factors for metastasis for small choroidal melanomas are being used to select treatment and counsel patients.² Consequently, there is a trend away from observation of some small melanocytic lesions and a trend toward earlier treatment of lesions that possess those risk factors.³ Updated results for treating uveal melanoma with plaque brachytherapy and charged particles have been published. This introductory chapter provides an overview of the methods of managing patients with ciliary body and choroidal melanoma. In the subsequent chapters, several authorities address the details of various therapeutic modalities.

The general concepts discussed here are based on more than 35-years’ experience with patients with posterior uveal melanoma who were managed on the Ocular Oncology Service at Wills Eye Hospital, combined with a review of the literature but it is not possible to quote all important contributions. Although an attempt has been made to be as objective as possible, the opinions expressed here are those of the authors and may not accurately reflect the opinions of others.

General considerations

Historically, enucleation was once considered to be the only appropriate management for a patient with a posterior uveal melanoma. Several years ago, however, some authorities challenged the effectiveness of enucleation for preventing metastatic disease and even proposed that enucleation may somehow promote or accelerate metastasis.^4,5 The validity of these arguments was challenged by others, who believed that early enucleation offered the patient the best chance of cure.^6,7 This controversy over enucleation was responsible for initiating a trend away from enucleation and the increasing use of more conservative therapeutic methods.

Depending upon several clinical factors, the most common methods of management today include observation, transpupillary thermotherapy (TTT), radiotherapy, local resection, enucleation, orbit exenteration, and various combinations of these methods. There is currently an increasing variety of methods to treat or prevent metastatic disease that are beyond the scope of this short chapter. The most frequently employed treatment methods today are radiotherapy and enucleation. The Collaborative Ocular Melanoma Study (COMS) was organized to address several issues related to uveal melanoma and important information has been obtained from that study.^8–12 Nevertheless, each case must be individualized and one should recommend the treatment that is believed to provide the best systemic prognosis, while preserving as much vision as possible. If possible, the patient should be referred to an ocular oncologist or other ophthalmologist who has experience in managing patients with posterior uveal melanoma.

Periodic observation

Some small melanocytic tumors are best managed by periodic fundus photography and ultrasonography to document growth of the lesion before recommending definitive treatment.¹³ Identified risk factors for metastasis include greater tumor thickness, tumor proximity to the optic nerve, presence of visual symptoms from the melanoma, and prior documented growth.^2,14 Since documented growth may be associated with a worse systemic prognosis, there is a trend to treat patients who have the other risk factors, without necessarily waiting for documentation of growth.³ Tumors that show highly suspicious features or unequivocal evidence of growth should generally have some form of active therapy, depending upon the factors mentioned previously.

Photocoagulation

Photocoagulation was once a commonly used method to treat small choroidal melanomas.^15–17 It was originally done with xenon photocoagulation but argon laser subsequently became more commonly employed. Studies showed that xenon photocoagulation achieved better tumor control but argon laser was associated with fewer complications.¹⁶ Recently, TTT has largely replaced argon laser for treating selected small melanomas that are less than 3 mm in thickness and located more than 3 mm from the foveola.¹⁸

Transpupillary thermotherapy

TTT is a recently popularized method of treating selected small and medium-sized choroidal melanomas.^18–20 It delivers heat to the tumor in the infrared range using a modified diode laser delivery system. It does not appear to produce as much damage to the sensory retina as does laser photocoagulation. Recent observations have clarified the limitations and complications of TTT.²⁰ It is used frequently as a supplement to plaque radiotherapy.²¹

Radiotherapy

Radiotherapy is still the most widely employed treatment for posterior uveal melanoma. The most commonly used form of radiotherapy has been the application of a radioactive plaque.^8–10,22,23 Several years ago, most melanomas were treated with a Cobalt 60 plaque.²⁴ More recently, Iodine-125 and Ruthenium-106 plaques have largely replaced Cobalt-60 at most institutions.^25–27 It was originally believed to be useful for small and medium-sized melanomas that were outside the retinal vascular arcade and posterior to the ora serrata. Although the COMS failed to address tumors in other locations, some studies have presented the rationale for using plaque radiotherapy for macular melanoma,²⁸ ciliary body melanoma,²⁹ large melanoma,²³ and melanoma with extrascleral extension.²²

Another method of radiotherapy is charged particle irradiation.^30–32 Although this technique was originally believed to provide a collimated beam that would limit the radiotherapy to the precise area of the tumor, this theory has not been substantiated by clinical experience. Similar complications occurred with radioactive plaques. It appears that survival, visual results, and complications are very similar with plaque and charged particle treatment.

On the basis of available information, it appears that patients treated with radiotherapy have a survival rate similar to those treated by enucleation.⁸ Furthermore, there is probably no significant difference between plaque radiotherapy and charged particle radiotherapy with regard to short-term and long-term complications. Studies have shown that between 5% and 10% of patients treated with radiotherapy ultimately require enucleation because of tumor recurrence or radiation complications.^33,34

Local resection

Local resection of melanomas involving the ciliary body and choroid continues to be popular in some centers.^15,35 We initially began using the technique of penetrating sclero-uveo-retinectomy (full-thickness eye wall resection) as advocated by Meyer-Schwickerath³⁶ and later popularized by Peyman and associates.³⁷ Although there are a number of potential serious complications, the eye can tolerate fairly extensive resections. More recently, we have employed a partial lamellar sclerouvectomy, a modification of the technique popularized by Foulds and Damato, in which the tumor is removed with the aim of leaving the retina and vitreous intact.¹⁵ Our surgical technique and results for this procedure are reported.^35,38,39

Local resection of a posterior uveal melanoma offers several theoretical advantages over enucleation and radiotherapy. In contrast to enucleation, it is designed to preserve vision and to maintain a cosmetically normal eye. In contrast to radiotherapy it has fewer long-term complications if the initial surgery is successful. However, it does have more potential immediate complications, such as vitreous bleeding, retinal detachment and cataract, while radiotherapy is almost never associated with such immediate complications. However, some degree of radiation retinopathy and cataract are common long-term complications of all forms of radiotherapy. There is no current evidence that local resection of posterior uveal melanomas is any different from enucleation or radiotherapy with regard to patient survival. There are fewer complications and better visual results for smaller, more anteriorly located tumors. More complications can be expected when larger post-equatorial tumors are managed in this manner.

Some authorities have reported experience with endoresection of choroidal melanoma, by removing tumor with a vitrectomy approach, and a few authorities are now using endoresection to remove choroidal melanoma after plaque radiotherapy or charged particle irradiation. Long-term follow-up will be necessary to determine the validity of endoresection techniques.^40,41

Enucleation

As mentioned earlier, the traditional method of treating uveal melanomas by enucleation was challenged several years ago.^4,5 Others continued to believe that enucleation was an appropriate method of management.^6,7 Enucleation is generally indicated for advanced melanomas that occupy most of the intraocular structures and for those that have produced severe secondary glaucoma. Another relative indication for enucleation is a melanoma that has invaded the optic nerve. Enucleation with a long section of the optic nerve seems more reasonable in such cases. However, many juxtapapillary melanomas, that have not actually invaded the nerve, can often be managed by custom-designed notched radioactive plaques.^42–45 The so-called “no touch enucleation” was introduced a number of years ago to minimize the amount of surgical trauma and theoretically to lessen the chance of tumor dissemination at the time of surgery.⁴⁶ An essential aspect of this technique was to freeze the venous drainage from the tumor prior to cutting the optic nerve. The “no touch” technique has recently fallen into disuse at most centers because it is cumbersome and its benefits are only theoretical. However, a very gentle standard technique of enucleation should be employed, without clamping the optic nerve prior to cutting it.

There have been recent advances in the types of orbital implants used following enucleation. The hydroxyapatite implant, designed to improve the ocular motility in patients undergoing enucleation, is still used widely,^47,48 but other motility implants have been introduced.

Pre-enucleation radiotherapy (PERT) has been advocated by some authorities. In general, this involves the use of 2000 cGy of external beam radiotherapy to the affected eye and orbit prior to enucleation. Data from the COMS have supported prior non-randomized studies that suggested that PERT is not advantageous over standard enucleation alone.¹¹

Orbital exenteration

The subject of orbital exenteration for uveal melanomas with extrascleral extension is also controversial.⁴⁹ It seems that complete orbital exenteration should not be done in cases of mild degrees of extrascleral extension. However, in the rare instance of massive orbital extension in a blind, uncomfortable eye, primary orbital exenteration is probably justified. In most instances of orbital extension of uveal melanoma, it is not necessary to sacrifice the skin of the eyelid. The eyelid-sparing exenteration skin provides a much better cosmetic appearance.⁵⁰

Management of systemic metastasis

Ideally, the best management of uveal melanoma would be to use method of preventing metastasis in the early stages of the intraocular disease.⁵¹ Unfortunately, there is no current method of achieving this. Once a uveal melanoma has metastasized to distant organs, the patient’s prognosis is poor. If the metastasis occurs as a solitary lesion, increased survival has been achieved with local resection of the metastatic focus.⁵² There is no current evidence that chemotherapy or immunotherapy are effective in the primary management of uveal melanomas. The vast majority of affected patients have no detectable evidence of systemic metastasis at the time of diagnosis of the uveal melanoma. Consequently, clinicians have not been inclined to employ such treatment.

Likewise, the role of chemotherapy and immunotherapy is unproved in the treatment of patients with systemic metastasis from uveal melanomas.^53,54 There is a possibility that such treatment may prolong survival for a few months but it is unlikely that it will be curative. Recent studies have provided hope that chemoembolization and immunoembolization may prolong survival⁵⁵ but further research is needed to determine their efficacy.

Counseling the patient

Regardless of the method of management selected by the clinician, it is important that the affected patient be informed of all available options. The expected results and potential complications should be explained to the patient and family members in detail. The patient should be informed of the availability of a second opinion from other physicians familiar with uveal melanoma. The final decision regarding management should be made by the patient with guidance of his or her physician.⁵⁶

Conclusion

This chapter has provided an update on some general principles of management of posterior uveal melanomas. Small asymptomatic melanocytic tumors of the posterior uvea that exhibit dormant features can probably be observed periodically without any treatment until definite evidence of growth is documented. Some small choroidal melanomas that were previously treated with photocoagulation are now being treated with newer techniques of transpupillary thermotherapy.

Radiotherapy can be employed using episcleral plaques or charged particle treatment. Selected melanomas of the ciliary body and peripheral choroid can be treated by local resection techniques. Local resection has theoretical advantages, but the surgery takes longer and the immediate complications are potentially greater.

Enucleation is generally indicated for most large melanomas greater than 15 mm in diameter and greater than 10 mm in thickness. It is also generally indicated for tumors that have invaded the optic nerve. It does not appear that pre-enucleation radiotherapy improves patient survival.

Orbital exenteration is justified for advanced uveal melanomas with massive extraocular extension. Its value in the management of smaller degrees of extraocular extension is uncertain. Such patients can often be managed by methods of radiotherapy. It currently appears that chemotherapy and immunotherapy do not provide a therapeutic cure for uveal melanomas but their true effectiveness awaits the results of further studies.