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Correction: Volume: 211 Pages: 233-233 DOI: 10.1016/j.ajo.2019.11.027 Published:‏ MAR 2020 PURPOSE: To validate a staging system for metastatic uveal melanoma that will facilitate planning, reporting, and interpreting the results of clinical trials. DESIGN: Reliability and validity study. METHODS: The performance index, the largest diameter of the largest metastasis and alkaline phosphatase level at the time of diagnosis of metastases, and overall survival of 249 patients from 7 ocular oncology centers who died of dissemination were analyzed. Predicted median survival time calculated according to the Helsinki University Hospital Working Formulation was used to assign patients to stages IVa, IVb, and IVc, which correspond to predicted survival times of >= 12

Purpose Ultraviolet-B (UV-B) radiation can cause phototoxic macular injuries in young people who have been sunbathing but not sungazing and in welders. Welders have a reportedly increased risk of uveal melanoma. We analyze phakic and pseudophakic risks for solar and welding arc UV-B exposure. Design Optical radiation measurement, analysis, and perspective. Methods Spectral transmittances were measured for UV-transmitting, UV-blocking, and blue-blocking intraocular lenses (IOLs). The photoprotective performances of crystalline and intraocular lenses were analyzed using relevant epidemiologic and laboratory data and action spectra for acute retinal phototoxicity and melanoma photocarcinogenesis. Results Crystalline lens UV-B retinal protection is deficient in children and young adults, increasing their potential susceptibility to acute retinal phototoxicity and hypothetical photomelanomagenesis. UV-B radiation has sufficient energy/photon to induce primary melanomagenic DNA lesions, unlike blue light or UV-A radiation. UV-blocking and blue-blocking IOLs have negligible UV-B transmittance. UV-transmitting IOL transmittance of UV-B radiation is equivalent to that of a 15-year-old crystalline lens. Conclusions If optical radiation exposure is responsible for welders' increased risk of uveal melanoma, then UV-B radiation is the most probable causative agent and spectacle wear is a potential confounding factor in epidemiologic studies of ocular melanoma. Welders under 30 years of age are at greater risk for welding maculopathy than older welders. Children, adults under 30 years of age, and pseudophakic individuals with UV-transmitting IOLs should wear sunglasses in bright environments because of the UV-B window in their crystalline lenses or IOLs.

Purpose To report rates of death and related outcomes through 10 years after treatment of large choroidal melanoma and to evaluate characteristics of patients and tumors as predictors of relative treatment effectiveness and time to death. Design Randomized multicenter clinical trial of pre-enucleation radiation vs enucleation alone conducted as part of the Collaborative Ocular Melanoma Study. Methods Eligible patients were free of metastasis and other cancers at enrollment. All patients were followed for 5 years or longer at scheduled examinations and contacts for metastasis, another cancer, or death. Each decedent was classified as having histopathologically confirmed melanoma metastasis, suspected melanoma metastasis without histopathologic confirmation, another cancer but not melanoma metastasis, or no malignancy. Results Within 10 years after enrollment, 576 of 1,003 patients died. Ten-year all-cause mortality rates were 61% for patients in both treatment arms. Ten-year rates of death with histopathologically confirmed melanoma metastasis were 45% in the pre-enucleation radiation arm and 40% in the enucleation alone arm. Older age and larger maximum basal tumor diameter were the primary predictors of time to death from all causes and death with melanoma metastasis. No differences in unadjusted or adjusted mortality rates were found between treatment arms. Of 448 patients eligible for 10 years of follow-up, 145 patients (32%) were alive and clinically cancer-free 10 years after treatment. Conclusions Longer follow-up confirmed the earlier report of no survival advantage attributable to pre-enucleation radiation. Mortality rates by baseline characteristics should facilitate counseling of patients who have large choroidal melanoma and no evidence of metastasis or another malignancy at diagnosis.

PURPOSE: To evaluate choroidal melanomas in enucleated eyes for the presence of type I estrogen receptors. METHODS: Fourteen consecutive eyes with large choroidal melanomas (defined as >16-mm basal diameter and >8 mm thickness) from 14 patients (eight women and six men with a mean age of 57 years; range, 25–74 years) enucleated in accordance with the Collaborative Ocular Melanoma Study (COMS) protocol were investigated. Immunohistochemical techniques were employed to label the choroidal melanomas for the presence of type I estrogen receptors. Each specimen was then evaluated in a masked fashion by an experienced ophthalmic pathologist for positive nuclear staining. RESULTS: No tumors showed immunohistochemical evidence of a type I estrogen receptor. CONCLUSION: Type I estrogen receptors are not present in choroidal melanoma. Estrogens are not likely to influence choroidal melanoma growth through traditional receptors.

To describe the principal histopathologic findings in a series of 1,527 globes with uveal melanoma and the relationship of these findings to each other.All eyes enucleated in the Collaborative Ocular Melanoma Study (COMS) were examined independently by three ophthalmic pathologists and the findings recorded on a data form. A composite of findings was obtained after adjudication.The diagnosis was choroidal melanoma in 1,527 (99.7%) of 1,532 cases examined. Misdiagnoses were metastatic adenocarcinoma (four) and hemangioma (one). Spindle cell (9.0%), mixed cell (86.0%), and epithelioid cell (5.0%) types were observed. Medium tumors were located more posteriorly than large tumors. Considerable local invasion was seen: rupture of Bruch's membrane (87.7%), invasion of the retina (49.1%), tumor cells in the vitreous (25.2%), vortex vein invasion (8.9%), invasion of tumor vessels by tumor cells (13.8%), and invasion into emissary canals (55.0%). Overall, 81.1% demonstrated local invasion, excluding rupture of Bruch's membrane. Scleral invasion was present in 55.7% of eyes, and extrascleral extension was present in 8.2%. Mitotic activity was significantly reduced in eyes that had received preenucleation radiation treatment (P.001). The number of macrophages in the tumor increased with increased pigmentation (P.001) and increased necrosis (P.01).The accuracy of diagnosis in the COMS is high, with histopathologic confirmation of the diagnosis at 99.7%. Extensive local invasion of the tumor was seen. Preenucleation irradiation significantly reduced the number of mitotic figures. An association was found regarding the presence of macrophages, the level of pigmentation, and degree of necrosis.

Purpose: To describe the baseline characteristics and status of patients enrolled in the Collaborative Ocular Melanoma Study (COMS) randomized clinical trial of pre-enucleation radiation of large choroidal melanoma conducted in the United States and Canada, and to compare characteristics of patients enrolled with those of patients with tumors of eligible size who were not enrolled in order to assess the generalizability of findings from the clinical trial. Methods: For all patients evaluated for the clinical trial at COMS centers from November 1986 through December 15, 1994, selected data were transmitted to the COMS Coordinating Center. For patients who enrolled in the clinical trial, ophthalmic and medical history, examination findings, and visual acuity measurements were recorded prior to enrollment. Standardized A-scan and contact B-scan echographic examinations were performed prior to enrollment, and photoechograms were submitted for central review for consistency with the diagnosis, independent measurement of the apical height of the tumor, and description of tumor configuration and internal reflectivity for each patient enrolled. Until January 1992, wide-angle fundus photographs and fluorescein angiograms taken prior to enrollment also were submitted for central review to confirm consistency with the diagnosis. All data were integrated and analyzed at the COMS Coordinating Center. Results: Of 6,078 patients with choroidal melanoma evaluated in COMS centers, 1,860 had tumors of eligible size; of these, 1,302 (70%) were eligible for the clinical trial, and 1,003 (77% of eligible patients) enrolled. The two principal reasons for ineligibility were other primary cancer and predominantly ciliary body melanoma. Ineligible patients were older than eligible patients, had larger choroidal melanoma, and had poorer visual acuity at the time of evaluation for the COMS (P Conclusions: The COMS clinical trial of pre-enucleation radiation was designed to yield internally valid treatment comparisons through random treatment assignment at time of enrollment. Findings also have high external validity because a majority (54%) of all patients with tumors of eligible size, and a large majority (77%) of all eligible patients, were enrolled. Furthermore, patient characteristics are similar to those of patients included in other evaluations of this method of treating large choroidal melanoma. Thus, findings from this clinical trial apply to all patients who have large choroidal melanoma and satisfy COMS eligibility criteria.

Purpose: To report initial mortality findings from the Collaborative Ocular Melanoma Study (COMS) randomized clinical trial of pre-enucleation radiation of large choroidal melanoma. Methods: Patients were evaluated for eligibility at one of 43 participating centers in the United States and Canada. Eligible consenting patients were assigned randomly at the time of enrollment to standard enucleation or to external radiation of the orbit and globe prior to enucleation. Eligibility was confirmed at the COMS Coordinating Center, Echography Center, and Photograph Reading Center. Adherence to the radiotherapy protocol was monitored at the Radiological Physics Center. The diagnosis of choroidal melanoma was confirmed following enucleation by a three-member Pathology Review Committee. Patient accrual began in November 1986 and was completed in December 1994; 1,003 patients enrolled. Patients have been followed at annual clinical examinations. Cause of death was coded by a Mortality Coding Committee whose members were not involved in the care of COMS patients; the clinical trial was monitored by an independent Data and Safety Monitoring Committee. Results: A total of 1,003 patients were enrolled; 506 were assigned to enucleation alone and 497 to pre-enucleation radiation. Treatment groups were well balanced on baseline characteristics. Only nine patients were found to be ineligible after enrollment, seven in the interval between randomization and enucleation and two after enucleation based on histopathology. All but nine patients were treated as assigned; in only six of 491 eyes treated with pre-enucleation radiation was there a major deviation from the radiotherapy protocol. With 5-year outcome known for 801 patients enrolled (80%), the estimated 5-year survival rates and 95% confidence intervals (CIs) were 57% (95% CI, 52% to 62%) for enucleation alone and 62% (95% CI, 57% to 66%) for pre-enucleation radiation. Among the baseline covariates evaluated, only age and longest basal diameter of the melanoma affected the prognosis for survival to a statistically significant degree. The risk of death among patients treated with pre-enucleation radiation relative to those treated with enucleation alone after adjustment for baseline characteristics of patients, eyes, and tumors was 1.03 (95% CI, 0.85 to 1.25). Of 435 deaths classified by the Mortality Coding Committee, 269 patients had histologically confirmed melanoma metastases at the time of death. Estimated 5-year survival rates for this secondary outcome were 72% (95% CI, 68% to 76%) for enucleation alone and 74% (95% CI, 69% to 78%) for pre-enucleation radiation. Conclusions: No survival difference attributable to pre-enucleation radiation of large choroidal melanoma, using the COMS fractionation schedule, has been demonstrated to date in this randomized trial. The trial had statistical power of 90% to detect a relative difference in mortality rates between the two treatment arms of 20% or larger. A smaller difference is possible, but a clinically meaningful difference in mortality rates, whether from all causes or from metastatic melanoma, is unlikely.

Purpose To trace the evolution and status of our knowledge of choroidal melanoma with regard to the nature, cause, and treatment of this tumor. Methods Historical materials beginning with Georg Bartisch's contributions in 1583 through to the Collaborative Ocular Melanoma Study and recent basic research are reviewed. Results Many individuals have made important contributions to our knowledge about this tumor. Basic information, however, regarding the natural history of the tumor, the most effective treatment, and its cause is lacking. Conclusion The Collaborative Ocular Melanoma Study will provide important information regarding the choice of treatment between enucleation and radiotherapy as well as natural history information, quality of life, and definitive pathology findings. Definitive treatment of choroidal melanoma will depend on knowledge of the genetic defects that cause the tumor. Within the next 25 years, it is predicted that genetic defects will be determined and tumor samples will be obtained using small-needle aspiration and DNA probes located on microchips. In addition, treatment will then be based on drugs designed to inhibit molecules related to the genetic defect in the tumor.

Silver staining of nucleolar organizer regions is an objective method for evaluating the malignancy of a variety of tumors. We studied 126 ciliochoroidal melanomas, three coincidental nevi that occurred in eyes with melanomas, and one magnocellular nevus collected from the Collaborative Ocular Melanoma Study to determine the effectiveness of the silver-stained nucleolar organizer region technique in assessing the malignant potential of these tumors. Malignant lesions demonstrated higher mean silver-stained nucleolar organizer region counts (4.347) than benign nevi (1.855) (P ≤ .0001). Among malignant melanomas, mixed-cell melanomas had slightly higher counts than spindle-cell melanomas (P ≤ .0001), but this difference was not important clinically. Results were also compared to other histopathologic variables, which disclosed correlation of silver-stained nucleolar organizer regions with mitoses and tumor size. Comparison with computerized cytomorphometric analyses of prognosis also disclosed significant correlation. This technique may prove to be a useful adjunct in the assessment of malignancy and treatment response of uveal melanomas.

Purpose To review emerging information related to changing concepts in the management of choroidal melanoma. Design and methods This perspective reviews and discusses selected studies from the past two decades that have influenced management strategies for large, medium, and small-size choroidal melanomas. Results Large choroidal tumors continue to be managed primarily by enucleation. The large tumor trial of the Collaborative Ocular Melanoma Study (COMS) demonstrated neither a positive nor negative effect on 5- and 8-year mortality rates among more than 1,000 patients whose eyes containing large choroidal melanomas were randomized to treatment between enucleation alone or enucleation preceded by external radiation. The medium-size tumor trial of the COMS randomized more than 1,300 patients between iodine-125 brachytherapy and enucleation. Mortality rates following brachytherapy did not differ from mortality rates following enucleation for up to 12 years after treatment. Iodine-125 has become the most commonly used isotope for brachytherapy in North America. Ten-year follow-up of eyes treated with helium ion and 20 years of experience with proton beam confirm the relative safety and efficacy of these modalities for treatment of choroidal melanoma. Although there is a trend toward earlier treatment of small melanomas, controversy exists regarding the indications for treatment as well as the choice of specific therapy. Recurrences of melanoma after eye-sparing treatment appear to be associated with an increased rate of metastatic disease. Effective adjunctive therapy to prevent or treat melanoma metastasis is lacking. Conclusions Choroidal melanoma is a lethal tumor. Although evidence suggests that patients with untreated choroidal melanomas have a poorer prognosis than patients who receive treatment, our current treatments are unable to prevent tumor-related deaths for many patients. The use of preoperative external radiation as an adjunct to enucleation for large choroidal melanomas is unsupported by data from the COMS trial. The use of radiation with either brachytherapy or charged particles for the management of medium-size choroidal melanomas is well supported on the basis of long-term follow-up studies. There is a trend toward treatment of smaller choroidal melanomas. Treatment of melanomas should be directed toward minimizing the potential for recurrences as recurrent melanomas are associated with an increased rate of metastatic disease. Gains in our ability to manage choroidal melanoma will likely be modest at best until effective systemic therapies can be identified.

PURPOSE: To report intraoperative echographic localization of iodine-125 episcleral plaque for brachytherapy of choroidal melanoma. METHODS: In a retrospective study, 117 eyes with medium-sized choroidal melanoma in 117 patients not participating in the Collaborative Ocular Melanoma Study underwent iodine-125 episcleral plaque radiotherapy with intraoperative echographic verification of plaque placement between January 1992 and December 1998 at the Bascom Palmer Eye Institute. RESULTS: After initial plaque placement using standard localization techniques, intraoperative echography demonstrated satisfactory tumor–plaque apposition in 76% of eyes (89 of 117). In the 28 eyes (28 of 117, 24%) that required repositioning of the plaque, the extent of misplacement was less than 1 mm in 10 eyes, 1.1 to 3.0 mm in six eyes, and greater than 3 mm in eight eyes. Two eyes had tilting of the plaque, and in two additional eyes, although the plaque covered all tumor margins, the centration was considered suboptimal. Repositioning was necessary in 1 eye with an anteriorly located tumor (1 of 13, 7.7%) and in 20 eyes with peripapillary or posterior pole tumors (20 of 67, 26.3%). Anteriorly located tumors required plaque repositioning significantly less frequently than did posteriorly located tumors (P = .041). Misalignment involved one tumor margin in 23 eyes and two margins in five eyes. The most commonly misaligned margins were the lateral (35%) and posterior margins (26%). In no case was an anterior marginal misalignment documented. At a mean follow-up of 37 months, no tumor-related death or metastatic disease was noted. Two of the 117 patients (1.7%) had local tumor recurrence and underwent enucleation. CONCLUSIONS: Intraoperative echography is an effective adjunct for localization and confirmation of tumor–plaque relationship. This technique facilitates the identification and correction of suboptimal plaque placement at the time of surgery, potentially minimizing treatment failures.

Median survival after diagnosis of liver metastasis from ocular melanoma is short and no satisfactory treatment options exist. This clinical trial evaluated isolated hepatic perfusion (IHP) for patients with this condition. Twenty-nine patients with unresectable liver metastases from ocular melanoma were treated with a 60-min hyperthermic IHP using 1.5 mg/kg of melphalan (mean total dose 105 mg). By means of laparotomy, perfusion inflow was established with a cannula positioned in an isolated segment of the retrohepatic inferior vena cava. Portal and infra-renal inferior vena cava blood flow was shunted externally to the axillary vein using a veno-veno bypass circuit. Patients were assessed for toxicity, radiographic response, and survival. There was no treatment related mortality and transient grade three-fourths hepatic toxicity was observed in 19 patients (65%). Mean length of operation and hospital stay was 8.3 hours and 10 days, respectively. There were 3 complete responses (10%) (duration: 12, 14+, 15 months) and 15 partial responses (52%) (mean duration: 10 months). The initial site of disease progression included liver in 17 (68%) of 25 patients who recurred. At median follow-up of 30.7 months, the median actuarial progression-free and overall survivals were 8 and 12.1 months, respectively. IHP with melphalan alone results in significant regression of established liver metastases for patients with ocular melanoma. However, after IHP, disease progression is most commonly observed in the liver, and survival after disease progression is short. On the basis of a pattern of tumor progression predominantly to the liver, continued clinical evaluation of hepatic directed therapy in the patient population is justified.—Hans E. Grossniklaus

Purpose To compare single-dose and fractionated-dose radiotherapeutic effects on choroidal melanoma cells. Methods We determined the effects of gamma radiation on OM431 cell survival by exposing cells to either a single 9-Gy dose or two 4.5-Gy fractionated doses at intervals of 20 minutes to eight hours. The effects of single dosing and fractionated dosing at six hours were compared at doses of 2 to 12 Gy. Results Tumor cell repair was most rapid during the first two hours. Maximum repair had occurred by six hours after radiation. Cell survival curves showed doses greater than 3 Gy of single-dose gamma radiation resulted in a greater number of cells killed than did equivalent fractionated doses. Conclusions Ocular melanoma in vitro is relatively radioresistant to low-dose fractionated radiotherapy. High single-dose radiotherapy would be more effective but would also result in more damage to normal tissue unless more focused modalities of radiotherapy are used.

Ocular melanoma has a unique metastatic predilection for the liver and is refractory to most forms of therapy. The dual blood supply of the liver with differential perfusion of metastatic lesions and normal hepatocytes by the hepatic artery and portal vein, respectively, has led to the evaluation of intrahepatic chemotherapy and chemoembolization in this disease. Despite suggestion of efficacy in phase II trials, this therapy has not been systematically evaluated. We conducted a randomized phase I/II trial evaluating escalating doses of intrahepatic chemotherapy with cisplatin with or without polyvinyl sponge (PVS) in 19 patients with ocular melanoma and liver metastases. The cisplatin dose was initiated at 100 mg/m and was increased in 25% increments. Patients were randomized to receive cisplatin alone or cisplatin plus PVS. Seven patients were treated with intrahepatic cisplatin at 100 mg/m: four with PVS, and three without. The dose was escalated to 125 mg/m with or without PVS in the remaining 12 patients. The maximum tolerated dose for intra-hepatic cisplatin was determined to be 125 mg/m with or without PVS. The overall response rate was 16%. Dose-limiting toxicities included renal, hepatic and haematological effects. This therapy produces a modest response rate in patients with ocular melanoma and liver metastases.

Background. Liver metastasis develops in approximately two-thirds of patients with recurrent uveal melanoma. Despite therapy, the median survival of those with liver metastasis is 5 to 7 months. The recognition of a grave prognosis associated with liver metastasis has led to evaluation of new modalities of therapy, including the use of regional therapies such as intrahepatic arterial chemotherapy and either embolization or chemoembolization of hepatic metastases. In this study, the results of an institutional experience over the past 2 decades are reviewed and prognostic factors that affect survival from the time the liver metastasis is diagnosed are assessed. Methods. In this study of 201 patients with uveal melanoma involving the liver who were treated at M. D. Anderson Cancer Center between 1968 and 1991, the authors retrospectively reviewed the cases and compared the results of systemic therapies, hepatic infra-arterial chemotherapies, and chemoembolization of liver metastases. Cox's multivariate analysis and stepwise logistic regression were then computed to determine significant prognostic variables. Results. The systemic therapies produced a response rate of less than 1%. Chemoembolization was the most effective treatment, inducing responses in 36% of patients. Survival curves were calculated using the life-table method of Kaplan and Meier. Patient-and tumor-related characteristics were examined and their relation to on survival from the time of diagnosis of liver metastasis was determined. Levels of serum alkaline phosphatase, total bilirubin, and lactic dehydrogenase plus response to treatment showed a strong relation to survival. In contrast, univariate analysis showed that patient age and gender, metastasis free interval, presence of extrahepatic metastasis, and type of therapy for liver metastasis did not influence survival. Multivariate stepwise regression analysis identified serum alkaline phosphatase and metastasis free interval as the main independent prognostic factors for survival after liver metastasis diagnosis. Conclusions. Of the three modalities of therapy used for choroidal melanoma metastatic to the liver, only chemoembolization using cisplatin-based regimens produced a meaningful response rate. Information from this analysis can be used to predict the outcome of patients with uveal melanoma metastatic to the liver. Patients with metastatic ocular melanoma confined to the liver should be treated with chemoembolization and should not be included in chemotherapy trials designed for cutaneous melanoma. Cancer 1995; 76:1665–70.

Uveal melanoma metastatic to the liver remains an incurable disease. Unlike colorectal carcinoma metastastic to the liver, surgery is not considered a first-line approach because of the diffuse, multifocal nature of the hepatic metastases. Systemic chemotherapy and immunotherapy regimens have had minimal efficacy for patients with metastatic ocular melanoma. Hepatic artery chemoembolization has been explored to a limited degree, but reports of response remain anecdotal. Hepatic arterial infusion with fotemustine had an overall response rate of 38%, but the overall survival is still disappointingly short. Isolated hepatic perfusion is a promising technique for this disease. Although the reported response rate is more than 60%, isolated hepatic perfusion is associated with potential morbidity, and the number of patients treated by this means is still limited. Percutaneous hepatic perfusion has the potential for less morbidity, and its efficacy in this clinical setting warrants further evaluation. The conclusion of this review is that current treatment modalities need further refinement and new ones need to be developed to improve the outlook for patients with uveal melanoma metastatic to the liver. Unlike cutaneous melanoma, which metastasizes to numerous sites, uveal melanoma commonly metastasizes only to the liver. This underscores the importance of developing effective forms of liver-directed therapy.—Hans E. Grossniklaus

A patient with malignant melanoma of the choroid and ciliary body had a primary cutaneous melanoma and the B-K mole syndrome phenotype. Because of this newly described association, all patients with the B-K mole syndrome (phenotype) should have a complete ocular examination to discover if there is any evidence of ocular melanoma. Likewise, all patients with ocular melanoma should have a thorough dermatologic examination to determine evidence of cutaneous melanoma and the B-K mole syndrome (phenotype).

We performed experiments to determine the potential usefulness of nuclear magnetic resonance spectra in the diagnosis and follow-up of ocular melanoma. High-resolution phosphorus 31 nuclear magnetic resonance spectra at 109.3 MHz were obtained for human uveal melanoma, Greene hamster melanoma, and normal human diploid fibroblast cells. Phosphate metabolites were identified and their concentrations were shown to vary among the different cell lines. Uveal melanoma cells contain unusually high concentrations of the phospholipid metabolite phosphorylcholine and the phosphodiesters glycerol 3-phosphoryl choline and glycerol 3-phosphoryl ethanolamine. Baseline data are thus provided for studies of the effect of various treatment modalities on uveal melanoma. These initial results suggest that the data provided by high-resolution phosphorus 31 nuclear magnetic resonance spectra can provide useful diagnostic and follow-up data with respect to ocular melanoma.

We studied radioactive metal compounds to determine their localization in malignant Greene melanoma in the eye of the Syrian golden hamsters. Scintigraphy of an ocular melanoma was achieved with several radioactive metals: radioactive (/sup 111/In)-bleomycin, radioactive gallium (/sup 67/Ga)-citrate, and radioactive lead (/sup 203/Pb)-tris. The /sup 111/In-bleomycin had the highest tumor uptake (5.45% dose/g), but not the highest tumor-to-background ratios. The /sup 67/Ga-citrate had a maximum tumor uptake of 4.87% dose/g at 48 hours. The /sup 111/In-chloride had a melanoma uptake of 2.26% dose/g, while with /sup 203/Pb-tris the uptake was 1.61% dose/g. These uptake ratios compare favorably with that of radioactive phosphorus (/sup 32/P) - 2.21% dose/g. Noninvasive localization of malignant melanoma in the eye was accomplished with metal isotopes. Detailed analysis of in vitro uptake data by tumor and background tissues revealed the optimum time for scanning and precluded unnecessary trials.

The occurrence of uveal and cutaneous malignant melanoma and the dysplastic nevus syndrome in the same individual suggests an etiologic relationship among these diseases. Thus, the dysplastic nevus syndrome could be viewed as marking an increased risk of both cutaneous and ocular melanoma. We postulated that if such a relationship exists, patients with both forms of melanoma should have a high prevalence of dysplastic nevi. We examined 44 patients (31 women and 13 men ranging in age from 20 to 80 years) with uveal melanoma for evidence of cutaneous melanoma and dysplastic nevi. We also examined photographs of 46 patients (24 men and 22 women ranging in age from 19 to 67 years) with nonfamilial cutaneous melanoma to determine the prevalence of dysplastic nevi. We found a 4.5% prevalence of dysplastic nevi in patients with uveal melanoma, significantly lower than the 41% prevalence in patients with cutaneous melanoma (two of 44 patients vs 19 of 46 patients). This study indicates that uveal and cutaneous melanoma are not etiologically linked through dysplastic nevi and suggests that patients with uveal melanoma are no more likely to have cutaneous dysplastic nevi than the general population.

We studied two patients, a 72-year-old man and a 27-year-old woman, with metastatic melanoma documented by cytologic examination of the ocular fluids. Neither patient had a clinically detectable ocular mass. Fine-needle aspiration with cytologic examination may be useful in the diagnosis of metastatic ocular melanoma.