Minoru Furuta

Metastasis of Uveal Melanoma Millimeter-by-Millimeter in 8033 Consecutive Eyes

OBJECTIVE To determine the rate of metastasis of uveal melanoma on the basis of tumor thickness in millimeters. METHODS Retrospective medical record review. RESULTS The mean (median) patient age was 58 (59) years. A total of 8033 eyes were examined. Of the 285 eyes with iris melanoma, the mean tumor thickness was 2.7 mm and metastasis occurred in 0.5%, 4%, and 7% at 3, 5, and 10 years, respectively. Of the 492 eyes with ciliary body melanoma, the mean tumor thickness was 6.6 mm and metastasis occurred in 12%, 19%, and 33% at 3, 5, and 10 years, respectively. Of the 7256 eyes with choroidal melanoma, the mean tumor thickness was 5.5 mm and metastasis occurred in 8%, 15%, and 25% at 3, 5, and 10 years, respectively. For all uveal melanoma, metastasis at 5, 10, and 20 years was 6%, 12%, and 20% for small melanoma (0-3.0 mm thickness), 14%, 26%, and 37% for medium melanoma (3.1-8.0 mm), and 35%, 49%, and 67% for large melanoma (>8.0 mm). More specifically, metastasis per millimeter increment at 10 years was 6% (0-1.0 mm thickness), 12% (1.1-2.0 mm), 12% (2.1-3.0 mm), 16% (3.1-4.0 mm), 27% (4.1-5.0 mm), 28% (5.1-6.0 mm), 29% (6.1-7.0 mm), 41% (7.1-8.0 mm), 50% (8.1-9.0 mm), 44% (9.1-10.0 mm), and 51% (>10.0 mm). Clinical factors predictive of metastasis by multivariate analysis included increasing patient age, ciliary body location, increasing tumor diameter, increasing tumor thickness, having a brown tumor, and the presence of subretinal fluid, intraocular hemorrhage, or extraocular extension. CONCLUSION Increasing millimeter thickness of uveal melanoma is associated with increasing risk for metastasis.

Proliferative Radiation Retinopathy after Plaque Radiotherapy for Uveal Melanoma

PURPOSE To determine risk factors, occurrence rate, management, and outcome of proliferative radiation retinopathy (PRR) after plaque radiotherapy for uveal melanoma. DESIGN Case-control study. PARTICIPANTS Three thousand eight hundred forty-one patients who underwent plaque radiotherapy for uveal melanoma were entered into the study. METHODS Retrospective review of medical records. MAIN OUTCOME MEASURES Proliferative radiation retinopathy after plaque radiotherapy for uveal melanoma. RESULTS Of 3841 eyes treated with plaque radiotherapy for uveal melanoma, PRR developed in 5.8% at 5 years and in 7% at 10 and 15 years using Kaplan-Meier analysis. The mean time to onset of PRR was 32 months (median, 30 months; range, 4-88 months). On univariate analysis, baseline factors predictive of PRR (P<0.05) included young age, diabetes, hypertension, Hispanic race, shorter tumor distance to the optic disc and to the foveola, Bruchs membrane rupture, choroidal location of the tumor, subretinal fluid, higher radiation dose to the optic nerve and to the foveola, higher radiation rate to the tumor apex and to the tumor base, additional transpupillary thermotherapy, and notched plaque. In the multivariate model, young age (odds ratio [OR], 1.44; 95% confidence interval [CI], 1.25-1.67, per decade decrease), diabetes mellitus (OR, 2.73; 95% CI, 1.69-4.40), and shorter tumor distance to the optic disc (OR, 1.10; 95% CI, 1.04-1.17) were related to the occurrence of PRR. The most common forms of management included panretinal photocoagulation (70%), vitrectomy (21%), and observation (17%). Resolution of the neovascularization was obtained in 63% of eyes after treatment. CONCLUSIONS Proliferative radiation retinopathy developed in 7% of eyes by 10 years after plaque radiotherapy for uveal melanoma. The main factors for development of PRR included young age, preexistent diabetes mellitus, and shorter tumor distance to the optic disc.

Iris melanoma: Features and prognosis in 317 children and adults

PURPOSE To evaluate iris melanoma in children versus adults. METHODS Retrospective, nonrandomized clinical case series including all patients with a clinical diagnosis of iris melanoma managed at the Ocular Oncology Service at Wills Eye Institute over 40 years. Patients were divided into three age categories based on age at presentation: children (≤ 20 years), mid-adults (21-60 years), and older adults (>60 years). The clinical features, treatments, and outcomes were statistically analyzed based on patient age at presentation. The main outcome measures were melanoma features and related metastasis and death. RESULTS Of 8,101 eyes with uveal melanoma, there were 317 (4%) with iris melanoma, including 24 (8%) children (≤ 20 years), 187 (59%) mid-adults (21-60 years), and 106 (33%) older adults (>60 years). There was no age-related difference in race, sex, tumor quadrant, thickness, pigmentation, associated corectopia, ectropion uveae, hyphema, or extraocular extension. Significant age-related differences were found with mean tumor basal diameter, tapioca appearance, mean intraocular pressure, secondary glaucoma, tumor seeding in angle, and mean number of clock hours of angle seeding. Multivariate analysis of factors predictive of metastasis included extraocular extension and high intraocular pressure. Factors predictive of death included increased tumor thickness and high intraocular pressure. There was no difference in metastasis or death by age group. CONCLUSIONS Iris melanoma shows significant clinical differences in children versus adults, with smaller tumor size, less tumor seeding in angle, and lower incidence of secondary glaucoma. There was no significant difference in metastasis or death by age group.

American Joint Committee on Cancer Classification of Uveal Melanoma (Anatomic Stage) Predicts Prognosis in 7731 Patients: The 2013 Zimmerman Lecture

PURPOSE To analyze the clinical features and prognosis of posterior uveal melanoma based on the American Joint Committee on Cancer (AJCC) (7th edition) tumor staging. DESIGN Retrospective interventional case series. PARTICIPANTS A total of 7731 patients. METHODS Uveal melanoma management. MAIN OUTCOME MEASURES Melanoma-related metastasis and death. RESULTS Of 7731 patients with posterior uveal (ciliary body and choroidal) melanoma, the AJCC tumor staging was stage I in 2767 (36%), stage II in 3735 (48%), stage III in 1220 (16%), and stage IV in 9 (<1%). Based on tumor staging (I, II, III, and IV), features that showed significant increase with tumor staging included age at presentation (57, 58, 60, 60 years) (P < 0.001), tumor base (8, 12, 17, 17 mm) (P < 0.001), tumor thickness (2.9, 6.0, 10.1, 10.2 mm) (P < 0.001), distance to optic disc (3, 5, 5, 5 mm) (P < 0.001), distance to foveola (3, 5, 5, 5 mm) (P < 0.001), mushroom configuration (6%, 24%, 34%, 33%) (P < 0.001), plateau configuration (3%, 4%, 7%, 11%) (P < 0.001), tumor pigmentation (48%, 53%, 69%, 78%) (P < 0.001), and extraocular extension (0%, 1%, 11%, 22%) (P < 0.001). After therapy, Kaplan-Meier estimates of metastasis at 1, 5, 10, and 20 years were <1%, 5%, 12%, and 20% for stage I, 2%; 17%, 29%, and 44% for stage II; 6%, 44%, 61%, and 73% for stage III, and 100% by 1 year for stage IV. Kaplan-Meier estimates of death at 1, 5, 10, and 20 years were <1%, 3%, 6%, and 8% for stage I; <1%, 9%, 15%, and 24% for stage II; 3%, 27%, 39%, and 53% for stage III, and 100% by 1 year for stage IV. Compared with stage I, the hazard ratio for metastasis/death was 3.1/3.1 for stage II and 9.3/10.1 for stage III. CONCLUSIONS Compared with uveal melanoma classified as AJCC stage I, the rate of metastasis/death was 3 times greater for stage II, 9 to 10 times greater for stage III, and further greater for stage IV. Early detection of posterior uveal melanoma, at a point when the tumor is small, can be lifesaving.

Influence of age on prognosis of young patients with uveal melanoma: a matched retrospective cohort study.

Purpose. To determine the influence of patient age on life prognosis in patients with uveal melanoma. Design. Matched retrospective cohort study of 122 patients in each age category (young [≤20 years], mid-adults [21–60 years], older adults [>60 years]). Results. Kaplan-Meier estimates of tumor-related metastasis at 3, 5, and 10 years were 1%, 8%, and 8% in young; 8%, 11%, and 26% in mid-adults; and 13%, 16%, and 24% in older adults. After exclusion of iris melanoma, Kaplan-Meier estimates of tumor-related metastasis at 3, 5, and 10 years were 2%, 11%, and 18% in young; 9%, 14%, and 21% in mid-adults; and 9%, 34%, and 33% in older adults. Risk factors for metastasis based on multivariate analysis included increasing age in young (p=0.05, hazard ratio [HR] 1.33), male gender in mid-adults (p=0.046, HR 4.23), and larger tumor basal diameter in mid-adults (p=0.002, HR 1.37) and older adults (p=0.001, HR 1.30). After adjusting for tumor diameter, the metastatic rate was lower in young patients compared to mid-adults (0=0.042, HR 3.00) and older adults (p=0.007, HR 4.20). Conclusions. Younger patient age at the time of diagnosis of uveal melanoma is associated with lower rate of metastasis compared to mid-adults and older adults.

Vitreous hemorrhage after plaque radiotherapy for uveal melanoma

Purpose: The purpose of this article is to determine the incidence, etiology, management, and outcome of vitreous hemorrhage (VH) after plaque radiotherapy for uveal melanoma. Methods: Retrospective review of medical records. Results: Of 3,707 eyes treated with plaque radiotherapy for uveal melanoma, VH developed in 4.1% at 1 year, 15.1% at 5 years, and 18.6% at 10 years by Kaplan–Meier analysis. Presumed causes of VH included tumor necrosis (29%), proliferative radiation retinopathy (24%), posterior vitreous detachment (16%), vascular occlusion (5%), and unknown (19%). Tumor necrosis was the most common cause of VH early in the follow-up period (3% at 1 year), while proliferative radiation retinopathy was the most common source of VH later (6.2% at 15 years). The most common initial management was conservative observation for resolution in 48%, laser photocoagulation in 24%, and vitrectomy in 18%. After a mean follow-up period of 5 years, the VH was completely resolved in 41%, partially resolved in 19%, unresolved in 20%, worsened in 5%, and enucleation was necessary in 15%. By multivariable analysis, risk factors for development of VH were the presence of diabetic retinopathy at first visit (relative risk, 6.64), shorter tumor distance to the optic disc (relative risk, 1.07), greater initial tumor thickness (relative risk, 1.1), and break in the Bruch membrane (relative risk, 2.93). The rates of local tumor recurrence, extraocular extension, and distant metastasis in 74 patients who underwent vitrectomy for VH removal after tumor regression were similar to those in patients who did not have vitrectomy for VH. Conclusion: Vitreous hemorrhage occurs after plaque radiotherapy for uveal melanoma in 15.1% of the patients by 5 years. The main factors predictive of VH included underlying diabetic retinopathy, closer tumor proximity to the disc, greater tumor thickness, and break in the Bruch membrane. After tumor regression, vitrectomy for blood removal appears to be safe.

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.