Current trends in the treatment of ocular melanoma by radiotherapy

The Collaborative Ocular Melanoma Study (COMS) has recently confirmed once and for all that it is safe to attempt to preserve an eye with a posterior uveal melanoma by demonstrating no survival advantage of enucleation over plaque radiotherapy. While COMS has been under way, we have set out in London to define the selection criteria for conservative therapy versus enucleation for the various categories of melanoma in terms of size, location within the eye, and presence or absence of retinal detachment. The evolution of this approach has culminated in an overall ocular survival rate of 94% in 597 patients following radiation therapy combined with a mean loss of visual acuity of only 2.4 Snellen lines in the eyes preserved.     

Long-term survival after ruthenium plaque radiotherapy for uveal melanoma. A meta-analysis of studies including 1,066 patients.

PURPOSE: Most case series of patients managed by brachytherapy for uveal melanoma are small and survival data show considerable inter-study variation. The aim of this study was to summarise similarly structured case series by meta-analysis. METHODS: A systematic review generated 5 similarly structured case series including survival data for 1,066 patients treated by ruthenium plaque radiotherapy for uveal melanoma. After assessing the inter-study clinical heterogeneity, data were weighed for study size and pooled. RESULTS: Patient and radiotherapy characteristics were largely homogenous, but tumour size varied considerably between studies. The 5-year melanoma-related mortality rate was 6% for small and medium tumours (T1/T2) and 26% for large (T3) tumours. The 5-year and 10-year melanoma-related mortality rates for a balanced set of tumours with small, medium and large tumours being present in similar proportions were 14% and 22%, respectively. CONCLUSION: Case series of patients with uveal melanoma managed by brachytherapy may be pooled to increase sample size and study power. The present estimate of survival following ruthenium plaque radiotherapy compares favourably with previously summarised data of survival after enucleation for similarly sized tumours.     

Survival following enucleation versus plaque radiotherapy in statistically matched subgroups of patients with choroidal melanomas: results in patients treated between 1980 and 1987

· Background: The relative effectiveness of plaque radiotherapy and enucleation in patients with choroidal or ciliochoroidal melanoma remains controversial. Most published comparative survival studies have evaluated clearly biased groups, short-term follow-up, or both. · Methods: The authors performed a retrospective, non-randomized, comparative survival study on 734 patients with a choroidal or ciliochoroidal melanoma treated by enucleation (n=237) or plaque radiotherapy (n=497) between July 1980 and June 1985, and on a residual group of 448 patients, 103 treated by enucleation and 345 treated by plaque radiotherapy, identified by variable-by-variable range matching. Melanoma-specific mortality and all-cause mortality were evaluated by the life-table method. · Results: The melanoma-specific mortality rate was substantially worse in the original enucleation subgroup throughout available post-treatment follow-up; however, differences in baseline prognostic factors between the subgroups are likely to explain much of the survival differential. After eliminating patients with nonoverlapping values of individual clinical variables to adjust for recognized intergroup differences at baseline, there was no significant difference in the mortality curves of the residual subgroups. The cumulative 15-year survival based on deaths from metastatic melanoma in the enucleation subgroup was 57.1% (standard error=6.4%), while that in the plaque radiotherapy subgroup was 61.8% (standard error=3.3%). · Conclusion: On the basis of these results, we conclude that a large difference in survival between equivalent groups of patients with primary choroidal or ciliary body melanoma treated by enucleation or by plaque radiotherapy appears unlikely. Received: 1 September 1998 Revised version received: 5 October 1998 Accepted: 26 October 1998     

Tumour location affects the incidence of cataract and retinopathy after ophthalmic plaque radiation therapy

AIM: To examine how tumour location affects ocular morbidity after ophthalmic plaque radiotherapy for uveal melanoma. METHODS: 69 eyes were irradiated and followed for a mean 42 months. There were 23 anterior uveal melanomas and 46 were posterior to the equator. Anterior and posterior tumours had similar basal dimensions. Their mean apical heights were 4.8 mm (anterior) and 3.5 mm (posterior) which received a mean 88 Gy and 83.4 Gy respectively. RESULTS: Only one patient (4%) plaqued for an anterior uveal melanoma developed secondary retinopathy (cystoid macular oedema). In contrast, 24 (52%) of the posterior choroidal melanoma patients developed retinopathy (p value <0.0001). Cataract developed in 18 (86%) eyes with phakic anterior tumour compared with seven (17%) eyes with posterior tumours (p value <0.0000). No posterior nasal tumours lost more than two lines of vision though 45% developed retinopathy. CONCLUSION: While plaque radiation of anterior melanomas is more likely to cause reversible vision loss secondary to cataract, treatment of posterior tumours is more likely to be associated with irreversible loss because of retinopathy. Nasal location is also protective against severe loss of vision.     

Alterations in expression of mucin, tenascin-c and syndecan-1 in the conjunctiva following retinal surgery and plaque radiotherapy

PURPOSE: Disturbances of the ocular tear film layer and dry eye symptoms are common complications following retinal surgery and ocular tumour therapy. Examined were the histopathological changes of the conjunctiva following posterior segment surgery and plaque radiotherapy. METHODS: Biopsy specimens of the superior bulbar conjunctiva were obtained during cataract surgery between 2 weeks and 7 years following vitrectomy (n=92) or plaque radiotherapy for uveal melanoma (n=20) and from control subjects without previous ocular surgery (n=29). These were examined using conventional histology (HE, PAS, Van Gieson) and immunochemistry [APAAP, using antibodies directed against MUC1, MUC5AC, syndecan-1 and tenascin-C (TN-C)]. The histopathological changes were graded and statistical analysis was performed using Wilcoxon and Kruskal-Wallis rank sum tests. RESULTS: Conjunctival specimens of patients following vitrectomy or plaque radiotherapy for uveal melanoma demonstrated increased epithelial stratification, a significant decrease in the number of PAS- and MUC5AC-positive goblet cells, and distributional changes in expression of MUC1, syndecan- and TN-C within conjunctival epithelium or stroma. These alterations - in particular the goblet cell reduction and stromal fibrosis - were most prominent in those patients who had undergone radiotherapy. CONCLUSIONS: Posterior segment surgery can lead to morphological alterations of the conjunctiva and distributional changes in ocular mucins, which may cause dry eye symptoms.     

Cataract surgery following cobalt-60 plaque radiotherapy for posterior uveal malignant melanoma

We reviewed the records of thirteen patients with posterior uveal malignant melanoma who had developed a mature radiation cataract following cobalt-60 plaque radiotherapy. Cataract extraction had been performed in seven of these patients as of the survey date of this investigation. We attempted to determine if cataract extraction increased the risk of metastatic melanoma, improved or worsened visual function, or resulted in any consistent intraoperative or postoperative complications that did not occur if the cataract was retained. Our analysis showed that removing the cataract did not appear to increase the risk of death from metastatic melanoma, but it also indicated that cataract extraction did not seem to improve the visual function of the irradiated eye. On the basis of our experience to date, we offer suggested guidelines for the management of patients who develop a mature cataract following cobalt-60 plaque radiotherapy of a posterior uveal malignant melanoma.     

Enucleation after plaque radiotherapy for posterior uveal melanoma. Histopathologic findings

A review of 1019 patients with posterior uveal melanomas, who were treated with episcleral plaque radiotherapy between April 1976 and December 1987, showed that 59 (6%) of these patients have thus far required enucleation of the affected eye. The most common clinical reasons for enucleation were tumor regrowth (51%) and neovascular glaucoma (31%). These irradiated melanomas were of mixed cell type in 40 cases (68%), spindle in 10 cases (17%), totally necrotic in 7 cases (12%), and epithelioid in 2 cases (3%). Some degree of tumor necrosis was seen in all cases. Overall, the median number of mitoses per 40 high-power fields in these irradiated tumors was 0. Most (64%) of the tumors had no identifiable mitosis in 40 high-power fields. A three-way simultaneous comparison of the following groups was made: irradiated eyes enucleated for tumor regrowth, irradiated eyes enucleated for neovascular glaucoma, and a matched group of nonirradiated posterior uveal melanomas. This comparison showed that the largest tumor dimension was significantly greater in the irradiated eyes enucleated for tumor regrowth than in the other two groups. Mitotic activity was significantly higher in the irradiated tumor regrowth and nonirradiated groups than in the irradiated neovascular group. There was no significant difference among the three groups in an analysis of height. The results suggested that mitotic activity may exist after plaque radiotherapy, especially when there is clinical evidence of tumor regrowth.     

New treatment modalities for uveal melanoma

The management of uveal melanoma has evolved tremendously for the past century, and more recently there is a trend toward more focal conservative treatment. Enucleation is still performed for large uveal melanoma when there is no hope for useful vision with conservative treatment. Plaque radiotherapy is particularly recommended for medium- or small-sized uveal melanoma. Special custom-designed plaque radiotherapy can be used for iris, ciliary body, or juxtapapillary choroidal melanoma. Charged-particle irradiation constitutes an alternative treatment modality for posterior uveal melanoma. However, charged-particle therapy is limited by the availability of appropriate therapeutic facilities. Local tumor resection using lamellar sclerouvectomy is mainly suitable for selected iris, ciliary body, or anterior choroidal tumors with smaller basal dimension and greater thickness. Ablative laser photocoagulation is indicated for very selected cases of small posterior choroidal uveal melanoma. Combined plaque radiotherapy with indirect ophthalmoscope laser therapy appears to be a more effective local tumor treatment plan than plaque radiotherapy alone. Transpupillary thermotherapy is the newest modality used as primary treatment or as complementary method to brachytherapy for treatment of selected choroidal melanomas. Hyperthermia with infrared irradiation below photocoagulation level produces tumor necrosis with few ocular complications. Based on the published ophthalmic literature, it seems that enucleation carries the same survival prognosis as each of the conservative treatment modalities.     

Uveal melanoma in teenagers and children. A report of 40 cases.

A review of 3706 consecutive patients with uveal melanoma revealed that 40 patients (1.1%) were age 20 years or younger at the time of diagnosis. The youngest patient was age 6 years but the majority of patients (78%) were between 15 and 20 years old. The tumor occurred in the iris in 5 cases (12%) and in the posterior uvea in 35 cases (88%). The mean largest tumor dimension and thickness was 10 mm and 5 mm, respectively. In all cases, the diagnosis of uveal melanoma was suspected before referral, and misdirected treatment was avoided. The tumor was initially treated by enucleation in 24 cases (60%), local resection in 7 (18%), plaque radiotherapy in 3 (8%), and observation in 6 (15%). Secondary treatment was required in 7 cases in the form of enucleation (4 cases), ablative laser (1 case), plaque radiotherapy (1 case), and exenteration (1 case). The mean follow-up period was 68 months (median, 48 months) from the time of treatment, and only one patient died of metastases (from a massive ciliochoroidal melanoma 33 months after treatment). The remainder of the group of young patients are alive and healthy. Cumulative survival rates show that 96% of young patients with uveal melanoma survive at the 5-year period.     

Ciliary body melanoma with limited nodular extrascleral extension and diffuse iris-angle infiltration treated by whole anterior segment plaque radiotherapy

Background Primary uveal malignant melanoma of the ciliary body associated with nodular extrascleral extension, diffuse iris-angle infiltration, and secondary glaucoma is usually treated by prompt enucleation. We report a patient with ciliary body melanoma associated with nodular extrascleral extension and diffuse infiltration of the iris and angle treated conservatively because the fellow eye was blind. Methods The clinical features and surgical management of a melanoma of the ciliary body with extrascleral extension and diffuse infiltration of the iris and angle are presented. The tumor was treated with focal I-125 plaque radiotherapy followed by supplemental whole anterior segment I-125 plaque radiotherapy. Results The patient has been followed for over 2.5 years since the initial plaque radiotherapy and over 1.5 years since the supplemental whole anterior segment radiotherapy. His visual acuity is correctable to 20/40 OD and there is no evidence of metastatic disease. His glaucoma is well controlled following trabeculectomy and tube shunt procedure. Conclusion Whole anterior segment plaque radiotherapy for ciliary body melanoma with diffuse iris-angle infiltration provided palliative local tumor control without significant local complications through available follow-up. Supported in part by: a grant from Research to Prevent Blindness, New York, NY to James J. Augsburger, MD; Chairman, University of Cincinnati, Department of Ophthalmology     

Bilateral primary choroidal melanoma treated with bilateral plaque radiotherapy: a report of three cases

PURPOSE: To report three cases of bilateral primary choroidal melanoma treated with bilateral plaque radiotherapy. METHODS: Retrospective, single-center case series. RESULTS: Case 1: In 1981, a 50-year-old man was diagnosed with a 5-mm-thick choroidal melanoma in the right eye (OD) and treated with plaque radiotherapy. In 1994, a 6.8-mm-thick choroidal melanoma in the left eye (OS) was treated with plaque radiotherapy. Final visual acuity was light perception OD and 20/20 OS at 24 years follow-up. Case 2: In 1983, a 53-year-old woman was diagnosed with a 3.5-mm-thick choroidal melanoma OS and treated with plaque radiotherapy. In 2001, an enlarging 2.5-mm-thick choroidal melanoma OD was treated with plaque radiotherapy. Final visual acuity was 20/30 OD and 20/20 OS at 22 years follow-up. Case 3: In 2001, a 92-year-old man was diagnosed with a 7.9-mm-thick choroidal melanoma OD treated with plaque radiotherapy. In 2003, an enlarging 2.8-mm-thick juxtapapillary choroidal melanoma was treated with plaque radiotherapy. Final visual acuity was 20/70 OD and 20/60 OS at 2.5 years follow-up. No patient showed ocular melanocytosis. Stable tumor regression was achieved in all six eyes. Metastatic disease did not develop in any case over 16 years of follow-up. CONCLUSIONS: Monitoring of both eyes of patients with uveal melanoma is important for the remote possibility of melanoma in the second eye. In these three patients, plaque radiotherapy allowed for preservation of the globes and some vision.     

Impact of enucleation versus plaque radiotherapy in the management of juxtapapillary choroidal melanoma on patient survival.

The records of 265 consecutive patients with juxtapapillary choroidal melanoma were reviewed and a statistical non-randomised retrospective study was performed to evaluate the risk for metastasis and compare the survival rate of patients treated with plaque radiotherapy or enucleation. To obtain sufficient overlap between the enucleation and plaque radiotherapy, the statistical analysis was limited to an adjusted subgroup of 127 patients who met eligibility criteria for plaque radiotherapy and who had a minimum of 3 years of follow up after treatment. In the adjusted subgroup of 127 patients, 92 patients (72%) were initially treated with enucleation and 35 (28%) with plaque radiotherapy. In both univariate and multivariate logistic analysis models, the age of the patient (> 50 years), tumour thickness (> 3 mm), and treatment by age interaction were found to be significant factors for development of distant metastasis. In patients younger than 50 years, the method of treatment (enucleation versus plaque radiotherapy) did not significantly affect the risk of metastasis. For those older than 50 years, there was a non-significant trend for patients in the enucleation group to be at a higher risk for metastasis than those in the plaque group. In the enucleation group, patients older than 50 years had a significantly higher incidence of distant metastasis than those younger than 50 years. In the plaque radiotherapy group, there was no significant higher incidence of metastasis in patients younger than 50 years than in those older than 50 years. When a Cox proportional hazards model was used to evaluate the survival rate, there was the same statistically significant effect of treatment by age interaction as was found in the multivariate logistic model on survival time. Moreover, there was a significant effect of treatment by tumour thickness interaction on survival time. Patients in the enucleation group had a better survival rate when the thickness of the tumour was less than 3 mm compared with a tumour of more than 3 mm. There were no apparent effects of tumour thickness on survival for patients treated with plaque radiotherapy. From these results, the authors currently recommend plaque radiotherapy as a viable option to enucleation in patients with juxtapapillary choroidal melanoma.     

Metastasis-free survival following treatment for uveal melanoma with either stereotactic radiosurgery or enucleation

PURPOSE: To determine whether metastasis-free survival following stereotactic radiosurgery is comparable with that following enucleation in a cohort of patients with choroidal and ciliary body melanoma. METHODS: This was a non-randomized, retrospective study of 196 patients with uveal melanoma treated between 1990 and 2000. A total of 118 eyes were enucleated and 78 eyes were treated with stereotactic radiosurgery. The following variables were recorded: age and sex of patient; tumour location, volume and height; the presence of retinal detachment, and extrascleral extension. Tumour location was divided into three categories: within the posterior pole; beyond the limits of the posterior pole but not including the ciliary body, and ciliary body location. Analysis of survival time was performed using Kaplan-Meier estimation of survival curves and Cox's proportional hazards regression modelling. RESULTS: The 5-year cumulative metastasis-free survival rate was 51% in the enucleation treatment group compared to 74% in the stereotactic treatment group. However, in the multivariate analysis there was no statistical difference in survival rates between the two treatment groups. The only variables that influenced survival rates were tumour location (p = 0.002), ciliary body tumours with the worst prognosis, and tumour volume (p = 0.001). CONCLUSIONS: Tumour size and location at presentation determined metastasis-free survival. Large ciliary body tumours had the highest risk of metastasis. Metastasis-free survival after stereotactic radiosurgery was comparable to that after enucleation.     

Hochdosisbrachytherapie des malignen Aderhaut- und Ziliarkörpermelanoms mit 106Ruthenium

BACKGROUND: The purpose of this study was to report the multifactorial results of high-dose (106)Ruthenium plaque brachytherapy for (cilio-)choroidal melanoma and to confirm them by histological examinations. PATIENTS AND METHODS: 100 patients with choroidal or ciliochoroidal melanoma treated by high-dose 106Ruthenium plaque brachytherapy were followed-up for 5 years. 12 secondary enucleated eyes were compared to a non-irradiated matched group by light microscopy. RESULTS: The 5-year local tumour control rate was 93%, the 5-year survival rate 91%. Late radiogenic side effects occured as a retinopathy in 13%, as an optic neuropathy in 5% and as a secondary glaucoma in 3% of the patients. 14% had to be enucleated, 10% developed metastases. The histopathologic examination revealed significantly higher degrees of necrosis (p=0,041), balloon cell degeneration (p=0,025) and fibrosis (p<0,001) in the irradiated melanomas than in the control tumours. CONCLUSION: High-dose 106Ruthenium plaque brachytherapy turned out to be an effective treatment procedure for posterior uveal melanoma (not exceeding a prominence of 5,5 mm) with a high rate of local tumour control and a low rate of side effects.     

The EORTC ophthalmic oncology quality of life questionnaire module (EORTC QLQ-OPT30). Development and pre-testing (Phase I-III)

AIMS: The research objective was to develop a questionnaire module to be used, in addition to the European Organisation into Research and Treatment of Cancer (EORTC) QLQ-C30, for measurement of quality of life (QL) among patients with uveal melanoma treated with methods such as transpupillary thermotherapy, plaque radiotherapy, proton beam radiotherapy, local resection, and enucleation. The present paper describes the development through Phases I-III. METHODS: Relevant QL issues were generated from literature search and from interviews with ophthalmologists, nurses, and patients with uveal melanoma representing three major treatment options: enucleation, plaque brachytherapy, and proton beam therapy. RESULTS: The provisional module was pretested in 61 patients from Finland, Sweden, and UK. The EORTC QLQ-OPT30 module consists of 26 items for all patients, and four additional items for patients receiving treatments other than enucleation. It measures ocular irritation, vision impairment, headache, worry about recurrent disease, problems with driving, problems with appearance functional problems due to vision impairment, and problems reading. CONCLUSIONS: Several treatment modalities are available for uveal melanoma. There is limited knowledge of the impact of these treatments on QL in the long and short term. We hope that the OPT30 module together with the EORTC QLQ-C30 core questionnaire can be a useful tool in research.     

Regression of Posterior Uveal Melanomas Following Cobalt-60 Plaque Radiotherapy

A method has been devised for evaluating the rate and extent of regression of the first 100 consecutive patients with a posterior uveal melanoma that we had managed by Cobalt-60 plaque radiotherapy at Wills Eye Hospital. It was found that the "average" posterior uveal melanoma in the series did not regress rapidly to a flat, depigmented scar but shrank slowly and persisted as a residual mass approximately 50% of the thickness of the original tumor at 54 months following Cobalt-60 plaque radiotherapy. We also found that the rate and extent of regression of the tumors in patients who subsequently developed metastatic melanoma were not appreciably different than the rate and extent of regression of the tumors in patients who remained well systemically. These observations indicate that the rate and extent of regression of posterior uveal melanomas following Cobalt-60 plaque radiotherapy are poor indicators of the prognosis of the affected patients for subsequent development of clinical metastatic disease.     

Plaque radiotherapy for the management of uveal metastasis

The management of uveal metastasis is focused on both the patient's systemic condition and the ocular condition. If there is evidence of systemic metastatic disease, then treatment of the nonocular and ocular metastatic tumors consists of chemotherapy, hormone therapy, immunotherapy, multiple-site radiotherapy, or observation. If there is no evidence of systemic involvement, then whole-eye treatment with chemotherapy, hormone therapy, immunotherapy, radiotherapy, or, rarely, enucleation is considered. For solitary uveal metastases, plaque radiotherapy is offered, and if the tumor is small, laser photocoagulation, resection, or thermotherapy can be used. Inactive uveal metastases are managed by periodic observation, but active uveal metastases often produce visual loss, secondary glaucoma, and pain, therefore, treatment is usually indicated. Radiotherapy is quite effective for control of most uveal metastasis. The technique of external beam radiotherapy is most often used and is delivered over a 3- to 4-week period in an outpatient setting. For those patients who fail chemotherapy, hormone therapy, immunotherapy, or external beam radiotherapy or those patients with a solitary uveal metastasis, plaque radiotherapy is an alternative method. Plaque radiotherapy is focal radiotherapy delivered to the eye in an inpatient setting over a relatively short period of approximately 3 days. Plaque radiotherapy provides satisfactory tumor control, even in eyes that fail other treatments. Side effects from plaque radiotherapy are comparable to those from external beam radiotherapy. Importantly, the plaque treatment requires less of a time commitment for these patients with a limited life expectancy.     

Cobalt plaque versus enucleation for uveal melanoma: comparison of survival rates.

Two hundred and twenty-three patients treated by cobalt plaque for uveal melanoma were compared with 416 patients treated by enucleation for uveal melanoma in terms of patient survival. The median follow-up time for the patients treated by cobalt plaque was 4.3 years. Kaplan-Meier survival curves were calculated up to five years following treatment based on time to tumour-related deaths. Cox's proportional hazards multivariate analysis was performed to determine which variables were related to melanoma-related deaths while controlling for age, size, and location of the tumours. Statistically significant predictive factors were location of tumour and largest tumour dimension. There was not a statistically significant difference in survival between patients treated by cobalt plaque and those treated by enucleation.     

Plaque radiotherapy for large posterior uveal melanomas (> or =8-mm thick) in 354 consecutive patients

OBJECTIVE: To assess treatment complications and tumor control after plaque radiotherapy for large posterior uveal melanomas measuring 8 mm or greater in thickness. DESIGN: Prospective noncomparative interventional case series. PARTICIPANTS: Three hundred fifty-four patients each of whom had a posterior uveal melanoma measuring 8 mm or greater in thickness treated with plaque radiotherapy. MAIN OUTCOME MEASURES: The four endpoints included (1) poor final visual acuity (20/200 or worse), (2) enucleation, (3) local tumor recurrence, and (4) metastasis. The clinical data regarding patient features, tumor features, and radiation parameters were analyzed for their impact on the four main outcomes using Cox proportional hazards regression models. RESULTS: Using Kaplan-Meier estimates, final visual acuity was poor in 57% at 5 years and 89% at 10 years follow-up. Using multivariate analysis, the most important risk factors for poor visual acuity included retinal invasion by melanoma, increasing patient age, iodine 125 (I(125)) isotope, and <2 mm distance to the optic disc. Treatment-related complications at 5 years included proliferative retinopathy (25%), maculopathy (24%), papillopathy (22%), cataract (66%), neovascular glaucoma (21%), vitreous hemorrhage (23%), and scleral necrosis (7%). Enucleation was necessary in 24% at 5 years and 34% at 10 years follow-up. Using multivariate analysis, the risk factors for enucleation included left eye, peripheral tumor margin anterior rather than posterior to the equator, increasing tumor thickness, and ruthenium 106 (Ru(106)) isotope. Using Kaplan-Meier estimates, local tumor recurrence was found in 9% at 5 years and 13% at 10 years follow-up. Using multivariate analysis, risk factors for tumor recurrence included Ru(106) radioisotope and ciliary body involvement with tumor. Tumor-related metastases were found in 30% at 5 years and 55% at 10 years follow-up. Using multivariate analysis, risk factors for metastases included inferotemporal meridian, anterior extension of the tumor to the iris root, increasing tumor base, and posterior margin < 2 mm from the optic nerve. CONCLUSIONS: Plaque radiotherapy provided tumor control at 10 years in 87% of patients with selected large posterior uveal melanomas (>8 mm thick) that otherwise would have been managed with enucleation. The large intraocular mass and associated features and radiation complications led to poor visual acuity in most patients. At 10 years follow-up, enucleation was necessary in 34% of patients, and metastasis developed in 55% of patients.