Choroidal Melanoma Resection.

Uveal melanoma is the most common intraocular malignant tumor, with the choroid being the most common site. Management of choroidal melanoma has evolved greatly over the past years. In the past, the conventional method of treatment was enucleation of the affected eye with a debate regarding the effect of enucleation to promote or prevent metastasis. However, nowadays, there are many therapeutic options available including plaque radiotherapy, proton beam radiotherapy, argon laser photocoagulation, transpupillary thermotherapy, stereotactic radiotherapy using gamma knife, enucleation, and surgical resection of the tumor whether through transscleral approach "Exoresection" or less commonly through internal resection approach "Endoresection." The indications and complications of each technique are reviewed. Although radiotherapy is the primary treatment of choroidal melanoma in most ocular oncology centers, it is used as an adjuvant therapy in combination with surgical resection. Preoperative stereotactic radiotherapy before endoresection and brachytherapy to the surgical bed in both exo and endoresection can effectively decrease the recurrence rate. In this article, we will focus on surgical resection of choroidal melanoma whether endoresection or exoresection. We collected data published in indexed journals and related books.

Introduction

There was a controversy regarding the effect of enucleation in treating patients with choroidal melanoma. Zimmerman and McLean proposed that tumor cells disseminate into systemic circulation during optic nerve cutting promoting distant metastasis,[12] however, other authorities challenged Zimmerman hypothesis believing that microscopic metastasis was already present before enucleation or even at time of diagnosis of melanoma.[34]

Therefore, there was always a need to develop an effective therapeutic alternative to enucleation aiming at better visual prognosis.

In the presence of multiple treatment options today including radiotherapy, transpupillary thermotherapy, enucleation, and surgical excision of the tumor, treatment should be highly individualized depending on several factors related to the tumor itself such as base diameter thickness, location of the tumor, involvement of the surrounding structures and tumor activity, and other factors related to the patient including patient's age, general health, status of the fellow eye, and psychological status of the patient.[5]

Each patient should be counseled about the nature of the disease, possible treatment options, possible risks, and expected outcomes.[6]

Surgical resection of choroidal melanoma was developed with the intent to save the eye, conserve as much useful vision as possible, and avoiding long-term complications of different methods of radiotherapy and cosmetic disfigurement associated with enucleation.

Although radiotherapy is the most commonly used modality nowadays in the treatment of choroidal melanoma in most centers, surgical resection may be the treatment of choice in selected patients.

Surgical resection of the tumor may be indicated as the primary treatment or can be used as a secondary treatment in certain situations as recurrence or toxic tumor syndrome.[7]

It can be used alone or with adjuvant radiotherapy decreasing rate of local recurrence.

Trans-Scleral Resection “exoresection”

In 1974, Peyman and Apple reported a case of left choroidal melanoma excised by localized full-thickness eye wall resection of the area overlying the tumor with preoperative application of xenon arc photocoagulation around the melanoma, with the intent to reduce the blood supply to the tumor decreasing the risk of bleeding, and then the eyewall defect was closed by scleral graft.[8]

Few years later, Peyman and Raichand shared more of his experience regarding this technique on a larger number of patients (19 patients) and showed promising results as 13 out of 19 patients retained useful vision implementing this technique as an alternative to enucleation in selected cases of choroidal melanoma.[9]

In 1984, Peyman et al. provided us with his 10-year experience using and improving this technique in 34 patients with an average follow-up period of about 5.3 years. He reported that no local recurrence had been observed and only two has distant metastasis after 3–4 years despite extensive surgical manipulation indicating the effectiveness of this treatment on long term.[10]

They suggested certain criteria for selection of cases who would benefit from eye-wall resection, including the following: tumor base diameter of no more than 16 mm and no more than one-third of the fundus is covered by an exudative retinal detachment, the distance between the mass and the optic disc is at least 3 mm, presence of clear media, no preoperative evidence of metastasis, and patient's medical fitness for general anesthesia.[910]

According to Peyman et al., the most suitable tumors for eye wall resection were those with base diameter of no more than 10 mm and their site is at the equator or anteriorly located, and the postoperative visual acuity depends largely on the site of the tumor.[910]

Later, a new technique was developed and adopted by many surgeons termed “Partial lamellar sclerouvectomy.”[1112]

It involves creation of circular, rectangular, or polyhedral-hinged partial-thickness scleral flap 4 mm around the site of the tumor after disinsertion of extraocular muscles. A scleral incision is done through the deep scleral layers surrounding the melanoma to expose the underlying normal uveal tissue which is subsequently incised to expose the underlying normal retinal tissue [Figure 1]. Gentle manipulations should be done at this stage in an attempt to excise the tumor together with inner scleral layer overlying it without disruption of the underlying retina or vitreous. Foulds et al. suggested blunt dissection with scissors between the retina and the tumor if they are firmly adherent to each other. However, Jager et al.[7] recommended the use of Bard-Parker scalpel instead of dissection with closed scissors in such cases claiming that it decreases the incidence of iatrogenic retinal injury and rhegmatogenous retinal detachment and residual tumor tissue can be treated with adjuvant radiotherapy. At the end of local resection, vitrectomy can be done, especially in the presence of iatrogenic retinal breaks. Finally, the defect is then closed by returning the outer scleral layer to its anatomical place and resuturing it with multiple interrupted sutures. The aim of this technique is resection of the tumor while preserving the neurosensory retina improving visual prognosis in such patients.[11121314]

Figure 1

External resection of uveal melanoma: Lamellar sclerouvectomy after lamellar scleral dissection the deep sclera is incised then the choroid opened and a blunt scissor is used to excise the deep sclera choroid and tumor as one mass

This technique was advocated by Shields et al.,[1112] Foulds et al.,[13] and Damato et al.[14]

Jager et al. suggested several modifications with the intent to decrease risk of operative complications including retinal breaks, rhegmatogenous retinal detachment, and postoperative diplopia.[7]

There is a risk of subretinal hematoma and a major intraoperative bleeding that may be difficult to control, therefore, it is usually preferred to be done under hypotensive general anesthesia.

Jager et al. suggested cauterization of the short posterior ciliary arteries around the tumor and claimed that this had markedly diminished the risk of bleeding.[7]

In 1991, Shields et al. reported their experience regarding partial uveal sclerouvectomy for 95 patients who were diagnosed with ciliary body and/or choroidal melanoma, 83% and 35% of patients developed vitreous and retinal hemorrhages, respectively, but fortunately, most of them underwent spontaneous resolution leaving fibrotic bands. Retinal detachment occurs in about 28% of patients, but surgery was required only in 16 patients (17%) and cataract developed in 34%, but it was mild and does not need any intervention. No reported orbital recurrences but enucleation was done because of residual or recurrent tumor in about 15 cases. Distant metastasis was reported in 5% of patients, 24% of patients have final postoperative visual acuity equal or better than preoperative visual acuity.[12]

Damato et al. reported incidence of rhegmatogenous retinal detachment after transscleral resection of choroidal melanoma in a prospective study including 156 patients to be 18% (28 eyes), 25 eyes were managed surgically for repair of retinal detachment with anatomic success was achieved in 84% of these patients. He noticed that retinal detachment is more common with thick tumors and male gender, and posterior extension of the tumor is a possible risk factor but of borderline significance.[15]

Transscleral resection can be combined with adjuvant ruthenium plaque radiotherapy with the intent to prevent tumor recurrence. Bechrakis et al. and Damato et al. concluded decreased risk of recurrence on long-term follow-up with the use of plaque radiotherapy as an adjuvant treatment.[1617]

Bechrakis et al. reported risk of local recurrence to be 24% and 32% after 5- and 10-year follow-up respectively. He also noticed that rate of recurrence increases with old age, large tumor basal diameter, and occurrence of retinal detachment. Lack of adjuvant ruthenium brachytherapy increases recurrence rate by 4.4 times.[16]

Kivela et al. compared the outcome of transscleral resection versus iodine brachytherapy in patients diagnosed with choroidal melanoma of thickness 6 mm or more. The rate of complications including macular edema, vitreous hemorrhage and cataract was higher in the brachytherapy group. Rubeosis iridis, neovascular glaucoma, and optic neuropathy occurred only with the brachytherapy group. Regarding final visual acuity, transscleral resection preserves 20/200 vision better than brachytherapy group, but the risk of local tumor recurrence was eight times higher in the surgical resection group than in the brachytherapy group. However, surprisingly, there was no statistical difference in the melanoma-specific survival over 8 years.[18]

The major cause of visual loss in patients diagnosed with choroidal melanoma treated with brachytherapy is radiation-induced maculopathy.[1920] However, many patients may develop neovascular glaucoma and exudative retinal detachment in response to irradiation which is presumed to be due to radiation-induced vasculopathy with leakage of inflammatory cytokines from compromised vasculature and production of vasogenic factors as a result of ischemia with subsequent development of rubeosis and neovascular glaucoma, a term known as “toxic tumor syndrome” was proposed.[2122]

Konstantinidis et al. reported a series of 12 patients diagnosed with toxic choroidal melanoma as a result of previous proton beam radiotherapy treatment, treated with transcleral resection and the results were encouraging. Eyes were conserved in 10 out of the 12 patients with flat retina, reasonable vision.[23]

Endoresection

It is less commonly performed than transscleral resection. It involves excision of the tumor after doing a complete 3-port pars plana vitrectomy including removal of posterior hyaloid and shaving of vitreous base [Figure 2]. If the tumor has invaded the retina, transretinal approach is done where the retina is excised along with the tumor. Otherwise, a retinal flap is created in a circumferential pattern around the tumor then a fluid may be injected through the retinotomy to detach the overlying retina. The surgeon then creates a choroidal incision and diathermy can be used to occlude choroidal vasculature surrounding the melanoma to decrease risk of bleeding. The tumor is then removed in a piecemeal technique using a vitrector leaving bare sclera at the site of the tumor.[24]. After tumor removal, the retina is meticulously examined and bleeding points should be identified and treated accordingly with endodiathermy. Any retinal break should be managed accordingly with any vitreous traction should be relived, subretinal fluid is drained through the choroidal defect, and once the retina becomes flat endolaser is applied to induce sterile chorioretinitis and adhesions around the choroidal coloboma. Silicone oil is usually used as a tamponading agent and can be subsequently removed after 3 months. It is advisable to apply cryotherapy to the scleral ports at the end of the surgery to destroy any seeded tumor cells preventing recurrence. Adjuvant plaque brachytherapy may be used, especially if the tumor margins are indistinct or if it has a peripheral extension.[24]

Figure 2

Endoresection of choroidal melanoma after gamma knife. Note the pale color of the optic disc and retina due to hypotensive anesthesia and high intraocular pressure and the white sclera at the bed of the resected tumor

Süsskind et al. recommended application of laser photocoagulation to the scleral bed after endoresection of the choroidal melanoma with the intent to destroy any residual tumor cells which may be responsible for future recurrences.[25]

Konstantinidis et al. reviewed the outcome of 71 patients who had undergone endoresection for choroidal melanoma. They concluded that endoresection is an effective measure in local tumor control where the rate of local recurrence was only 3%, and 31% of patients retain vision of 6/30 or better after a mean follow-up of 4.1 years.[26]

The patients included in this study were having the melanoma extending within two disc diameters of optic disc in about 61% of cases and involving the optic disc in 34% of cases. Therefore, according to this study, primary endoresection can be considered as a better option than brachytherapy in patients diagnosed with juxtapapillary choroidal melanoma.[27]

Tumors located posteriorly close to the optic disc are among the most difficult to manage because radiotherapy is associated with increased risk of optic neuropathy and transscleral resection is technically difficult. Thus, endoresection represents a good option in such cases.

However, there is a rising concern about the risk of tumor dissemination as a result of surgical manipulation leading to local recurrences or distant metastasis.[272829]

Damato et al. reported a case of choroidal melanoma for which transretinal internal resection was done. However, few years later, the patient was enucleated and a nodule was discovered close to the optic nerve which appeared to be local recurrent tumor encapsulated by scleral lamellae.[27]

Endoresection can be combined with adjuvant ruthenium brachytherapy in treatment of selected cases aiming for decreasing risk of recurrence. Brachytherapy in these cases is assumed to destroy any remaining viable intrascleral tumor cells that may escape endoresection as well as provide adequate irradiation to the resection margin if it was inadequate.

In large choroidal melanoma, radiotherapy carries an increased risk of optic neuropathy, cataract, radiation retinopathy, or even toxic tumor syndrome. Furthermore, these tumors are difficult to be resected completely with a significant risk of recurrence.

Hence, combining both techniques together would provide a better chance for local tumor control and decreasing recurrences.

Süsskind et al. evaluated the efficacy of this technique on 35 patients who were not candidates for plaque brachytherapy treatment alone, so this technique was implemented as an alternative to enucleation. The survival rate was about 68.6% with five patients died because of melanoma metastasis. They observed increased risk of metastasis with monosomy 3. The rate of local tumor recurrence was 22.9%, the rate of metastasis was 20%.[25]

Recently, Garcia-Arumi et al. evaluated the long-term results for patients diagnosed with high posterior choroidal melanoma treated with internal resection. The study included 41 patients, 21 of them received adjuvant plaque radiotherapy and the mean follow-up period was 102.5 months. The rate of local tumor recurrence was 12.2% (five patients), none of them received adjuvant radiotherapy.[30]

A new technique was developed by Bechrakis et al. for treatment cases of thick choroidal melanoma close to optic disc or macula. It includes application of proton beam radiotherapy followed few days later by internal resection of the melanoma.[31]

In 2009, Bechrakis et al. published their experience in surgical resection of large choroidal melanoma. The study included 292 patients, 150 of them were treated by exoresection and adjuvant ruthenium brachytherapy, while the rest were treated by proton beam radiotherapy followed by internal resection of the melanoma. The mean follow-up time was 30 months. The probability of local melanoma control in 5 years was 76% and 98%, respectively. The rate of distant metastasis in 5-year was 28% and 21%, respectively.[32]

Cassoux et al. evaluated effectiveness of endoresection technique in treatment of toxic choroidal melanoma so that it decreases the risk of rubeosis and neovascular glaucoma.[33]

A novel technique of radiotherapy of uveal melanoma is stereotactic radiotherapy based on the concept that ionizing radiation from different directions is focused on the tumor delivering a high dose of these ionizing radiation to the tumor with little effect on the surrounding tissues.[34]

Stereotactic radiotherapy is usually delivered by Leksell Gamma Knife with convergence of all gamma knife beams onto the tumor.

Schilling et al. evaluated the efficacy of internal resection of large melanoma with preoperative application of stereotactic radiotherapy using. The results were encouraging raising the concept of using this technique as an eye salvage procedure alternative to enucleation in large melanoma. This case series was conducted on 46 patients diagnosed with large uveal melanoma, 87% of them retain a good vision equal to or better than 20/200.[35]

Preoperative stereotactic radiotherapy or proton beam irradiation renders endoresection more safe since the tumor is removed piecemeal with the vitrectomy probe with possible dispersion of viable tumor cells. By applying preoperative gamma knife or proton beam, the tumor cells are destroyed, and in such case, intraoperative fragmentation of the tumor will disperse irradiated or necrotic cells and not viable ones.

Conclusion

Surgical resection of melanoma whether internal resection or exoresection is one of the most important measures improving prognosis with effective local tumor control if done appropriately in selected patients, especially when used with adjunctive radiotherapy or with preoperative stereotactic radiotherapy.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.