Uveal Melanoma Metastasis to the Contralateral Eye Structures: A Retrospective Comparative Analysis of 13 Consecutive Patients.

PURPOSE: To report uveal melanoma (UM) metastasis to the contralateral ocular and periocular structures. DESIGN: Retrospective study. PARTICIPANTS: Thirteen patients with UM metastasis to the contralateral ocular and periocular structures were included. METHODS: Clinical records were reviewed retrospectively. MAIN OUTCOME MEASURES: The development and time to onset of contralateral ocular and periocular metastasis, systemic metastasis, and death. RESULTS: Of the 13 000 treated UM patients, 13 patients were diagnosed with UM metastasis to the contralateral ocular and periocular structures. Mean patient age at primary UM diagnosis was 60 years (median, 60 years; range, 37-87 years). The primary uveal melanoma was in the choroid (n = 11) or ciliary body (n = 2) and was treated with brachytherapy (n = 11), proton beam radiotherapy (n = 1), or enucleation (n = 1). Systemic metastasis developed in 11 patients (85%) at a mean of 66 months (median, 34 months; range, 12-216 months) after diagnosis of the primary UM. All 11 patients (100%) showed liver metastasis and 8 patients (62%) also showed extrahepatic metastasis. The sites of metastasis to the contralateral ocular or periocular structures included the choroid in 4 patients (31%), the orbit in 7 patients (54%), and the eyelid in 2 patients (15%). One patient with eyelid metastasis demonstrated concurrent conjunctival nodule. Mean time to diagnosis of contralateral ocular or periocular metastasis was 94 months (median, 48 months; range, 9-375 months). Contralateral choroidal metastasis was multifocal in 3 of 4 patients (75%). Of 7 patients with orbital metastasis, 5 showed extraocular muscle involvement with restricted ocular motility. Treatment for contralateral choroidal metastasis included brachytherapy (n = 2), transpupillary thermotherapy (n = 1), and observation (n = 1). Treatment for contralateral periocular (orbit or eyelid) metastasis was excision (n = 5), external beam radiotherapy (n = 2), and observation (n = 2). Of 13 patients, death was documented in 11 patients at a mean of 17 months (median, 9 months; range, 3-54 months) as a result of systemic UM metastasis (n = 10) or unrelated cause (n = 1). CONCLUSIONS: Metastasis resulting from UM to the contralateral ocular and periocular structures is rare and generally occurs in patients with disseminated metastasis. Orbital tissue is the most common site of involvement, and these patients have short life expectancy.

INTRAVITREAL MELPHALAN FOR TREATMENT OF VITREOUS SEEDING FROM CHOROIDAL MELANOMA.

PURPOSE: To report treatment of vitreous seeding of choroidal melanoma with monthly injections of intravitreal melphalan. METHODS: Case report. RESULTS: A 70-year-old white woman noted floaters in her left eye, and further examination revealed visual acuity of 20/30 in both eyes. Funduscopically, there was a mushroom-shaped choroidal melanoma in her left eye, measuring 9 mm in basal dimension and 4.8 mm in thickness. Notably, there was apical retinal invasion of melanoma with mild vitreous hemorrhage, without vitreous seeding. The tumor was treated with iodine-125 plaque radiotherapy using an apex dose of 70 Gy over 99 hours, designed to include the retinal invasion. The melanoma demonstrated complete regression into a nearly flat scar of 1 mm and remained stable over 4 years. Five years after radiotherapy, there were diffuse vitreous pigmented seeds of presumed melanoma origin, emanating from the site of retinal necrosis. This progressively worsened over the following 18 months, suspicious for viable melanoma cells, as visual acuity concurrently declined to 20/100. Treatment with intravitreal melphalan (10 µg/0.05 mL) was delivered on a monthly basis for 12 cycles, resulting in vitreous seeds regression, and preservation of the eye. Final visual acuity was 20/200. There were no treatment-related complications. CONCLUSION: Intravitreal melphalan can be considered in cases of vitreous seeding from uveal melanoma.

Nomogram for visual acuity outcome after iodine-125 plaque radiotherapy and prophylactic intravitreal bevacizumab for uveal melanoma in 1131 patients.

AIMS: To develop a nomogram for prediction of visual acuity outcome following plaque radiotherapy for uveal melanoma. METHODS: Retrospective review of uveal melanoma treated with plaque radiotherapy and prophylactic intravitreal bevacizumab injections at 4-month intervals for 2 years duration. Two nomograms for poor visual acuity outcome (Snellen <20/200) were developed based on (1) Clinical risk factors. (2) Or clinical and treatment risk factors. RESULTS: There were 1131 included cases. The most important clinical risk factors (points for nomogram) for poor visual acuity outcome included subretinal fluid involving four quadrants (100), tumour thickness >4 mm (69), presenting visual acuity ≤20/30 (65), non-Caucasian race (58), tumour shape mushroom, bilobed, or multilobulated (57), and insulin-dependent diabetes (54). Risk of poor visual acuity at 2 years and 4 years increased from 11% and 24% with 40 points to 97% and >99% with 304 points. A second analysis was performed using both clinical and treatment risk factors. The most important factors included presenting visual acuity ≤20/30 (100), tumour largest basal diameter >11 mm (80), radiation dose rate to tumour base ≥164 cGy/hour (78), tumour thickness >4 mm (76), insulin-dependent diabetes (75) and abnormal foveolar status by optical coherence tomography at presentation (72). Risk of poor visual acuity at 2 years and 4 years increased from 6% and 14% with 56 points to 88% and 99% with 496 points. CONCLUSIONS: A nomogram using clinical or treatment risk factors can predict visual acuity outcome following plaque radiotherapy and prophylactic intravitreal bevacizumab for uveal melanoma and is available online at https://fighteyecancer.com/nomograms/.

Circumscribed Choroidal Hemangioma: Visual Outcome in the Pre-Photodynamic Therapy Era versus Photodynamic Therapy Era in 458 Cases.

PURPOSE: To analyze visual outcomes after treatment of choroidal hemangioma in the pre-photodynamic therapy (PDT) era versus PDT era. DESIGN: Retrospective, comparative case series. PARTICIPANTS: A total of 458 patients with circumscribed choroidal hemangioma. METHODS: Comparison of hemangioma managed in the pre-PDT (1967-2001) era versus PDT (2002-2018) era. MAIN OUTCOME MEASURE: Visual acuity outcome. RESULTS: A total of 458 tumors were treated over this 51-year period. A comparison (pre-PDT [n = 220 cases] vs. PDT [n = 238 cases]) revealed PDT era patients were of older mean age (48.9 vs. 53.8 years, P = 0.002) and were more likely to have systemic hypertension (17.7% vs. 33.8%, P < 0.001), tumor location in the macula (57.4% vs. 67.5%, P = 0.01), subretinal fluid on OCT (33.3% vs. 70.7%, P = 0.01), and greater extent of overlying lipofuscin (P = 0.001). Findings of tumor basal diameter and thickness and fluorescein and indocyanine green angiography were no different in the 2 eras. Treatment (pre-PDT vs. PDT) included argon laser photocoagulation (42.1% vs. 0.4%), PDT (0% vs. 43.8%), transpupillary thermotherapy (0% vs. 0.4%), plaque radiotherapy (7.0% vs. 5.2%), external beam radiotherapy (1.4% vs. 1.3%), enucleation (0.9% vs. 0.4%), and observation (48.6% vs. 47.6%). After treatment, patients in the PDT era demonstrated better mean logarithm of the minimum angle of resolution visual acuity (1.28 vs. 0.51, P < 0.001) (Snellen equivalent 20/400 vs. 20/63, P < 0.001). Final visual acuity was ≥20/40 for those with entering vision of ≥20/40 (59.6% vs. 74.7%, P = 0.001) and for those with entering vision of 20/50-20/200 (25.4% vs. 47.3%, P < 0.001). CONCLUSIONS: Management of choroidal hemangioma in the PDT era has allowed for significantly better visual outcome compared with the pre-PDT era, with mean final visual acuity of 20/400 (pre-PDT era) versus 20/63 (PDT era).

PHOTODYNAMIC THERAPY AS PRIMARY TREATMENT FOR SMALL CHOROIDAL MELANOMA.

PURPOSE: To report outcomes of photodynamic therapy (PDT) as primary treatment for small amelanotic choroidal melanoma. METHODS: Retrospective interventional case series of 12 patients with small choroidal melanoma treated with standard-fluence PDT (83 seconds; 50 J/cm) using verteporfin. OUTCOME MEASURES: Tumor regression, subretinal fluid resolution, best-corrected visual acuity, and PDT complications. RESULTS: There were 12 eyes with melanoma, demonstrating amelanotic (10 [83%]) or lightly pigmented (n = 2, 17%) appearance. The mean tumor thickness was 2.7 mm (median, 2.8; range 1.8-3.7 mm). After PDT, mean follow-up was 56 months (median, 53; range, 14-91). Outcomes revealed complete tumor regression after 1 session (n = 3, 25%), 2 sessions (n = 3, 25%), and 3 sessions (n = 2, 17%) of PDT, reduced to mean thickness of 2.1 mm (median, 2.0; range 1.2-3.4 mm). Tumors that failed to regress (n = 4, 33%) were further controlled with transpupillary thermotherapy (n = 1) or plaque brachytherapy (n = 3). Subretinal fluid, present in six eyes, demonstrated resolution (n = 5) or progression (n = 1), and one tumor developed new subretinal fluid after PDT (n = 1). Visual outcome was stable (n = 11 eyes) or improved (n = 1). Photodynamic therapy complications included local retina pigment epithelium atrophy at the site of treatment in 3 (25%) eyes, with no effect on macular or optic nerve function. CONCLUSION: Primary PDT resulted in complete tumor regression of small amelanotic choroidal melanoma in 67% at mean 5 years, with no major effect on visual acuity.

EXTRAOCULAR EXTENSION OF CILIOCHOROIDAL MELANOMA AFTER TRANSSCLERAL FINE-NEEDLE ASPIRATION BIOPSY.

PURPOSE: To describe development of extraocular extension of ciliochoroidal melanoma after transscleral fine-needle aspiration biopsy (FNAB) for cytogenetic studies. METHODS: Transscleral FNAB was performed for cytogenetic analysis of melanoma using a long 27-gauge needle attached to a 10-mL syringe by connector tubing entering obliquely through the sclera overlying the tumor base. An iodine 125 radioactive plaque was immediately applied to the sclera over the tumor and biopsy site after FNAB. PATIENTS: One patient with large ciliochoroidal melanoma of the right eye. RESULTS: Cytogenetic analysis of the melanoma revealed monosomy of chromosome 3. On examination, 18 months after plaque radiotherapy, there was regression of the tumor; however, a few small subepithelial pigmented lesions were noted in the conjunctiva close to the FNAB site. Excisional biopsy of the conjunctival pigmented lesions with 3 mm margins and with supplemental cryotherapy to the surrounding conjunctival margins and to the underlying sclera was performed. Histopathologic evaluation showed an oval nodule composed of a mixture of spindle and epithelioid cells deep within the substantia propria consistent with extraocular extension of uveal melanoma. Magnetic resonance imaging of the orbits showed no evidence of orbital involvement. This is the only case of extraocular extension developing among 408 consecutive transscleral biopsies (0.2%) performed at our center for cytogenetic or cytopathologic analysis. CONCLUSION: Although rare, transscleral FNAB of ciliochoroidal melanoma can lead to extraocular extension of the tumor through the biopsy site. Possible techniques to reduce the risk of this problem are discussed.

Primary transpupillary thermotherapy for choroidal melanoma in 391 cases: importance of risk factors in tumor control.

PURPOSE: To report the long-term outcome of primary transpupillary thermotherapy (TTT) for choroidal melanoma. DESIGN: Retrospective review of medical records. PARTICIPANTS: We included 391 patients with choroidal melanoma treated between 1995 and 2012 at the Oncology Service, Wills Eye Hospital, Philadelphia. METHODS: We delivered TTT with an infrared diode laser. MAIN OUTCOME MEASURES: Local tumor recurrence, Snellen visual acuity after TTT, and distant metastasis. RESULTS: Of 391 patients, 311 (80%) were treated from 1995 to 2000 and 80 (20%) from 2001 to 2012. Tumors in the 2001 to 2012 group were ultrasonographically thinner (2.2 vs. 2.7 mm), more distant from the optic disc (3.2 vs. 2.5 mm) and foveola (4.0 vs. 2.0 mm), were less often located in the macular area (14% vs. 40%), and had lower rates of acoustic hollowness on B-scan ultrasonography (63% vs. 84%), subretinal fluid (58% vs. 90%), and orange pigment (50% vs. 70%). Kaplan-Meier estimates for tumor recurrence in the 1995 to 2000 group were 29% at 5 years and 42% at 10 years, whereas estimates for tumor recurrence in the 2001-2012 group were 11% at 5 years and 15% at 10 years. Of 108 recurrent tumors 20 were controlled with additional TTT and 62 required plaque radiation (n=60) or proton beam radiation (n=2), with enucleation necessary in 26 patients. Tumor recurrence correlated with the number of high-risk tumor features: 10-year recurrence was 18% in those with 1 or 2 risk factors, 35% in those with 3 to 5 factors, and 55% in those with 6 or 7 factors. On multivariate analysis, features predictive of tumor recurrence were presence of symptoms (P<0.001), shorter distance between the tumor and the optic disc (P=0.026), subretinal fluid (P=0.035), thickness of residual tumor scar (P<0.001), and elevation of residual tumor scar (P<0.001). The only factor predictive of extraocular tumor extension was intraocular tumor recurrence after TTT treated with additional TTT (P=0.007). Presence of orange pigment before TTT (P=0.019), tumor recurrence (P=0.002), and extraocular tumor extension (P=0.017) were predictive of distant metastasis. CONCLUSION: This study shows a direct correlation between a larger number of high-risk tumor features and higher rates of tumor recurrence after primary TTT of (small) choroidal melanoma. We advise that, when possible, small choroidal melanomas with multiple risk factors be treated with methods other than TTT.

Circumscribed Choroidal Hemangioma.

Circumscribed choroidal hemangiomas are benign vascular hamartomas without systemic associations. Generally, they are orange-red elevated masses, which are found posterior to the equator. Lesions are usually solitary and unilateral. Overlying subretinal fluid, serous retinal detachment and cystoid macular edema are common findings. Intravenous fluorescein angiography, indocyanine green angiography, ultrasonography, optical coherence tomography and enhanced depth imaging are helpful ancillary tests for diagnosis of circumscribed choroidal hemangiomas. Asymptomatic circumscribed choroidal hemangiomas do not require treatment. For symptomatic lesions with exudative retinal detachment or cystoid macular edema, photodynamic therapy has emerged as the treatment of choice with high rates of tumor regression, subretinal fluid resorption and minimal complications. Lens-sparing external beam radiotherapy, plaque brachytherapy, proton beam therapy, stereotactic radiosurgery, transpupillary thermotherapy, laser photocoagulation and anti-VEGF injections are other treatment modalities.

Association of ocular and oculodermal melanocytosis with the rate of uveal melanoma metastasis: analysis of 7872 consecutive eyes.

IMPORTANCE: Ocular/oculodermal (oculo[dermal]) melanocytosis is a congenital periocular pigmentary condition that can lead to the development of uveal melanoma, estimated at 1 in 400 affected patients. In this study, patients with melanocytosis who developed uveal melanoma were found to have double the risk for metastasis compared with those without melanocytosis. OBJECTIVE: To determine the relationship of oculo(dermal) melanocytosis to the prognosis of patients with uveal melanoma. DESIGN, SETTING, AND PATIENTS: Retrospective chart review of 7872 patients with uveal melanoma treated at the Ocular Oncology Service, Wills Eye Institute, from August 25, 1970, through August 27, 2008. EXPOSURES: Enucleation, plaque radiotherapy, local resection, or thermotherapy. MAIN OUTCOMES AND MEASURES: Metastasis and death. RESULTS: Of 7872 patients with uveal melanoma, oculo(dermal) melanocytosis was present in 230 (3%). The melanocytosis involved the sclera (92%), iris (17%), choroid (12%), eyelid (8%), and temporal fossa (1%). Eyes with melanoma and oculo(dermal) melanocytosis had a relative risk for metastasis 1.6 times greater compared with those with no melanocytosis (P < .001). Metastasis of uveal melanoma was 2.8 times higher in patients with iris melanocytosis (P < .001), 2.6 times higher with choroidal melanocytosis (P = .02), and 1.9 times higher with scleral melanocytosis (P < .001). By Kaplan-Meier estimates, metastasis in patients with oculo(dermal) melanocytosis vs no melanocytosis was 2% vs 1.8% at 1 year, 27% vs 15% at 5 years, and 48% vs 24% at 10 years (P < .001). By multivariable analysis, the factors predictive of metastasis in patients harboring uveal melanoma associated with oculo(dermal) melanocytosis were increased tumor thickness (P = .001) and the presence of subretinal fluid (P = .05), and the only factor predictive of death was increased tumor thickness (P = .009). CONCLUSIONS AND RELEVANCE Patients with uveal melanoma associated with oculo(dermal) melanocytosis have double the risk for metastasis compared with those with no melanocytosis. All patients with oculo(dermal) melanocytosis should undergo ophthalmic examination and imaging on a twice-yearly basis because this could help with the early detection of melanoma.

Plaque radiotherapy for juxtapapillary choroidal melanoma: tumor control in 650 consecutive cases.

PURPOSE: To evaluate treatment of juxtapapillary choroidal melanoma with plaque radiotherapy and to investigate the role of supplemental transpupillary thermotherapy (TTT). DESIGN: Retrospective, comparative case series. PARTICIPANTS: We included 650 consecutive eyes with juxtapapillary choroidal melanoma within 1 mm of the optic disc. METHODS: Eyes with juxtapapillary choroidal melanoma receiving plaque radiotherapy over a 31-year period from October 1974 to November 2005 were included in the study. The TTT and no TTT groups were analyzed separately and compared. MAIN OUTCOME MEASURES: Local tumor control, metastasis, and tumor-related mortality. RESULTS: The median basal tumor diameter was 10 mm (range, 1.5-21) and median thickness was 3.5 mm (range, 0.5-14.8). In 481 eyes (74%), the tumor was directly adjacent to the optic disc and in 169 eyes (26%) the posterior tumor margin was between 0.1 and 1.0 mm from the optic disc. The circumpapillary extent of the tumor was <4 clock-hours in 321 eyes (50%), 4-8 clock-hours in 250 eyes (38%), and >8 clock-hours in 79 eyes (12%). Plaque radiotherapy using iodine-125 in 616 eyes (95%), cobalt-60 in 19 eyes (3%), iridium-192 in 12 eyes (2%), and ruthenium-106 in 3 eyes (<1%) delivered a median radiation dose of 8000 cGy (range, 3600-15 500) to the tumor apex and adjunctive TTT was used in 307 eyes (56%). Kaplan-Meier estimates for tumor recurrence, metastasis, and death were 14%, 11%, and 4% at 5 years and 21%, 24%, and 9% at 10 years, respectively. Eyes treated with additional TTT showed slight (statistically nonsignificant) reduction in recurrence and metastasis. Using multivariable analysis, factors predictive of tumor recurrence included foveolar tumor requiring TTT (hazard ratio, 5.07; P<0.001) and greater tumor thickness (hazard ratio, 1.29 per mm increase; P<0.001). Factors predictive of metastasis included greater tumor base (hazard ratio, 1.21 per mm increase; P<0.001) and increasing intraocular pressure (hazard ratio, 1.11 per mmHg increase; P = 0.020). CONCLUSIONS: Plaque radiotherapy for juxtapapillary melanoma provides local tumor control in approximately 80% of eyes at 10 years. In subjects who received TTT, there was slight but nonsignificant improved local tumor control and lower metastatic rate.

Tumor-related lipid exudation after plaque radiotherapy of choroidal melanoma: the role of Bruch's membrane rupture.

PURPOSE: To identify the risk factors predictive of development of tumor-related lipid exudation (TRLE) after plaque radiotherapy of posterior uveal melanoma. DESIGN: Case-control study. PARTICIPANTS: Cases included 294 patients with posterior uveal melanoma who had developed TRLE after plaque radiotherapy. Controls included 294 patients with posterior uveal melanoma who had not developed TRLE after plaque radiotherapy. Controls were matched with cases for age, gender, and initial tumor thickness. METHODS: Data were extracted from medical charts containing demographic, clinical, and treatment information. Detailed fundus drawings and color fundus photographs were reviewed for each patient. MAIN OUTCOME MEASURES: Tumor and ocular features of eyes with posterior uveal melanoma treated with plaque radiotherapy. RESULTS: Multivariate analysis identified Bruch's membrane rupture (P<0.001), serous retinal detachment (RD) before radiation (P< or =0.019), closer proximity to the optic disc and foveola (P = 0.004 and 0.013, respectively), greater tumor base (P = 0.035), failure to receive transpupillary thermotherapy (TTT) after radiation (P<0.001), and initial increase of serous RD after radiation (P<0.001) as significant risk factors predictive of development of TRLE after plaque radiotherapy of posterior uveal melanoma. Radiation dose at the tumor base correlated with maximum extent of TRLE (P = 0.003). The mean interval between plaque radiotherapy and onset of TRLE was 14 months (median, 11 months; range, 2-97 months), with 88% of cases developing TRLE within 2 years of radiation. The interval between the onset of TRLE and the first evidence of its regression was a mean of 33 months (median, 38 months; range, 2-194 months). CONCLUSIONS: Our study identified Bruch's membrane rupture as an important factor predisposing to development of TRLE after plaque radiotherapy of posterior uveal melanoma. Other predictive factors included serous RD before radiation, large tumor basal diameter, posterior tumor location, lack of adjunctive TTT, and early increase of serous RD after plaque radiotherapy.

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, Bruch's 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.

Giant choroidal nevus clinical features and natural course in 322 cases.

PURPOSE: Evaluation of clinical features and natural course of giant choroidal nevi (diameter >or=10 mm). DESIGN: Retrospective observational case series. PARTICIPANTS: We included 322 eyes of 322 patients. METHODS: Clinic-based study of tumor features, tumor outcome, and vision outcome. Kaplan-Meier analysis was used to assess time to transformation into melanoma. Cox proportional hazards regressions evaluated clinical factors predictive of nevus transformation into melanoma and nevus-related decreased vision (defined as <20/20 and unrelated to other eye pathology). MAIN OUTCOME MEASURES: Transformation of giant choroidal nevus into melanoma and nevus-related decreased vision. RESULTS: A medical record review of 4100 patients diagnosed with choroidal nevus identified 322 (8%) giant choroidal nevi. Median nevus basal diameter was 11 mm (range, 10-24). Median thickness was 1.9 mm (range, 0-4.4). Related retinal findings included drusen overlying nevus (n = 261 [81%]), subretinal fluid (n = 26 [8%]), orange pigment (n = 4 [1%]), retinal pigment epithelial (RPE) detachment (n = 6 [2%]), hyperplasia (n = 48 [15%]), fibrous metaplasia (n = 48 [15%]), atrophy (n = 63 [20%]), or trough (n = 6 [2%]). Kaplan-Meier analysis estimated transformation into melanoma in 13% at 5 years and 18% at 10 years. Multivariate analyses revealed factors predictive of transformation into melanoma including involvement or close proximity to the foveola (P = 0.017) and acoustic hollowness (P = 0.052). Nevus-related decreased vision was found in 2.2% of eyes at initial visit and 3.7% at final visit (median 41 and mean 61 months follow-up). Factors associated with nevus-related decreased vision at initial visit included subretinal fluid (P = 0.001), involvement or close proximity to foveola (P = 0.005), RPE detachment (P = 0.033), and nevus-related choroidal neovascular membrane (P = 0.044). Factors predictive of nevus-related decreased vision at final visit included involvement or close proximity to the foveola (P = 0.001) and presence of symptoms at the initial visit (P = 0.032). CONCLUSIONS: Giant choroidal nevi can clinically resemble choroidal melanoma but show features of chronicity, such as overlying drusen and RPE alterations. Over time, 18% transformed into melanoma, underscoring the importance of life-long surveillance.

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.

Plaque radiotherapy for juxtapapillary choroidal melanoma overhanging the optic disc in 141 consecutive patients.

OBJECTIVE: To evaluate tumor control with plaque radiotherapy for juxtapapillary choroidal melanoma that overhangs the optic disc. METHODS: Retrospective medical record review of 141 consecutive patients with data on complications of treatment, final visual acuity, visual loss, enucleation, tumor recurrence, metastasis, and death. RESULTS: The median patient age was 61 years. Presenting symptoms included reduced visual acuity in 72 eyes (51%), photopsia in 14 (10%), and visual field defect in 18 (13%); 35 patients (25%) were asymptomatic. The median tumor basal diameter was 11 mm and the median thickness was 5.2 mm. The tumor overhung 50% or less of the disc in 88 eyes (62%) and more than 50% of the disc in 53 eyes (38%). In 19 cases (13%), the tumor overhung the entire disc. All patients were treated with plaque radiotherapy, using a notched design in 126 eyes (89%) and a round design in 14 eyes (10%), with iodine 125 in 132 eyes (94%) and cobalt 60 in 9 eyes (6%). The median radiation dose to the tumor apex was 8500 cGy. Adjuvant transpupillary thermotherapy was used in 54 eyes (39%). During a mean follow-up of 56 months, complications included nonproliferative retinopathy in 61 eyes (51%), proliferative retinopathy in 26 (22%), maculopathy in 44 (37%), papillopathy in 57 (48%), neovascular glaucoma in 23 (19%), and vitreous hemorrhage in 48 (40%). A final visual acuity of 20/200 or worse was measured in 72 eyes (77%), and visual loss of more than 5 Snellen lines occurred in 59 eyes (63%). Enucleation was necessary in 27 eyes (23%). Tumor recurrence was found in 12 eyes (10%). Metastasis developed in 15 patients (13%) and death in 4 cases (3%). CONCLUSIONS: Using plaque radiotherapy for choroidal melanoma overhanging the optic disc, local tumor control was achieved in 90% of cases. Tumor and radiation effects led to poor visual acuity in 77% of eyes. The metastatic rate was 13% and the mortality rate was 3%.

Early macular morphological changes following plaque radiotherapy for uveal melanoma.

PURPOSE: To evaluate the time of onset and risk factors for the development of macular edema following plaque radiotherapy for uveal melanoma, using optical coherence tomography (OCT). METHODS: This observational case series included 135 consecutive patients with uveal melanoma treated with Iodine(125) plaque radiotherapy and adjunctive transpupillary thermotherapy (TTT) laser. Patients were evaluated at baseline and 6-month intervals following treatment using ophthalmoscopy, B-scan ultrasonography, fundus photography, and OCT. RESULTS: Median follow-up was 24 months. The mean time to onset of macular edema by OCT was 12 months. Median best-corrected logMAR visual acuity at the time of onset of OCT-evident macular edema was 0.3 (equivalent to 20/40 Snellen). The development of OCT-evident macular edema was significantly associated with maximum tumor thickness (P = 0.0016), largest tumor base (P < 0.0001), radiation dose, and dose-rate to the tumor base (P = 0.0315 and P = 0.0204, respectively). Neither radiation dose to the foveola nor treatment with adjunctive TTT laser was significantly associated with the development of macular edema. CONCLUSIONS: OCT is useful in the early detection of radiation-induced macular edema, before clinical signs of radiation maculopathy develop and before substantial visual loss occurs. The development of macular edema is significantly associated with larger initial tumor size.

Retinal break and rhegmatogenous retinal detachment after transpupillary thermotherapy as primary or adjunct treatment of choroidal melanoma.

OBJECTIVE: To report the development of retinal break or rhegmatogenous retinal detachment (RRD) after transpupillary thermotherapy (TTT) as primary or adjunct treatment of choroidal melanoma. METHODS: In this noncomparative, interventional case series, the authors reviewed medical records of 13 patients who developed retinal break or RRD following TTT. The main outcome measures were clinical features and outcome of treatment of retinal break or RRD following TTT. RESULTS: Of 1574 patients managed on the Oncology Service at Wills Eye Institute with TTT as primary or adjunct treatment of choroidal melanoma, 13 (1%) developed retinal break with or without RRD. The mean patient age at diagnosis of choroidal melanoma was 56 years. Treatment for choroidal melanoma included combined plaque radiotherapy and TTT in 10 patients and TTT alone in 3 patients. The median number of TTT sessions before development of retinal break or RRD was 2. Retinal break or RRD developed at a median of 3 months following the last TTT. All the retinal breaks were located in the TTT-treated area. Retinal breaks were atrophic in 11 eyes and horseshoe shaped in 2 cases. The extent of retinal detachment was none in 1 eye, 1 quadrant or less in 5 eyes, 2 or 3 quadrants in 4 eyes, and 4 quadrants in 3 eyes. Seven patients underwent vitrectomy, one received cryotherapy and laser photocoagulation, and five were observed without treatment. In all eight patients who received treatment for RRD, the retina was attached after a mean follow-up period of 54 months with no intraocular or local extraocular tumor dissemination. CONCLUSIONS: Development of retinal break or RRD is a rare complication of TTT for treatment of choroidal melanoma. The majority of these cases develop within 6 months of TTT and most are caused by atrophic retinal holes in the TTT-treated area.

Plaque radiotherapy for choroidal melanoma encircling the optic disc (circumpapillary choroidal melanoma).

OBJECTIVE: To report results of plaque radiotherapy for choroidal melanoma that completely encircles the optic disc (circumpapillary melanoma). METHODS: Retrospective medical record review over a 31-year period of 37 consecutive patients. The main outcome measures were treatment complications, long-term visual acuity, enucleation, tumor recurrence, metastasis, and death. RESULTS: The median patient age at treatment was 69 years (range, 20-86 years). The presenting complaint was visual loss in 19 eyes (51%), photopsia in 5 (14%), and visual field loss in 3 (8%). All tumors touched and encircled the optic disc for 360 degrees . The quadrantic location of the main tumor epicenter was superior in 8 eyes (22%), nasal in 10 (27%), inferior in 9 (24%), and temporal in 10 (27%). The median tumor basal diameter was 11 mm (range, 4.8-20 mm) and median tumor thickness was 3.6 mm (range, 1.8-14.8 mm). The optic disc was obscured to some extent by overhanging tumor in 19 cases (52%). The most commonly used isotope for plaque radiotherapy was iodine 125 (n = 34 cases; 92%), and a notched plaque design was used in 34 cases (92%). Planned adjunctive treatment included transpupillary thermotherapy in 17 cases (49%) and argon laser photocoagulation in 6 of 35 cases (17%) with follow-up. Of the 28 eyes with more than 5 months' follow-up (mean, 52 months; median, 46 months; range, 5-234 months), treatment complications included nonproliferative and proliferative retinopathy in 11 (39%) and 7 eyes (25%); maculopathy in 7 (25%); papillopathy in 9 eyes (32%); neovascular glaucoma in 5 (18%); and vitreous hemorrhage in 13 (46%). Pars plana vitrectomy was required in only 2 of 13 eyes (15%) with persistent vitreous hemorrhage. Long-term visual acuity of 20/200 or worse was observed in 13 eyes (62%), and 12 eyes (57%) lost more than 5 Snellen visual acuity lines, excluding 7 cases (25%) in which enucleation was necessary. Recurrence was noted in 4 cases (14%), of which 3 were treated with enucleation and 1 with transpupillary thermotherapy. Systemic metastasis occurred in 1 patient (4%) and there were no melanoma-specific deaths during the study period. CONCLUSIONS: Custom-designed plaque radiotherapy is a potential treatment for selected patients with circumpapillary choroidal melanoma. We found satisfactory local tumor control, and globe retention was achieved in 75% of eyes with more than 5 months' follow-up.

Iodine 125 plaque radiotherapy as salvage treatment for retinoblastoma recurrence after chemoreduction in 84 tumors.

PURPOSE: To assess tumor control and complications of iodine 125 (I125) plaque radiotherapy for retinoblastoma recurrence after chemoreduction (CRD). DESIGN: Interventional retrospective case series. PARTICIPANTS: Children with retinoblastoma treated on the Oncology Service, Wills Eye Hospital, initially examined from July 1994 to April 2005. METHODS: Eighty-four retinoblastomas with solid recurrence after CRD were treated with custom designed I125 plaque radiotherapy. Eyes with vitreous or subretinal seed recurrence were excluded. The CRD regimen included vincristine, etoposide, and carboplatin for 6 cycles plus local consolidation with thermotherapy or cryotherapy. The only alternatives to plaque radiotherapy in these cases would have been external beam radiotherapy (EBRT), additional chemotherapy, or enucleation. MAIN OUTCOME MEASURES: Tumor control and radiation complications. RESULTS: Tumor control was achieved in 95% of eyes by 5 years follow-up. Of the 59 recurrent tumors after CRD alone, 56 (95%) were controlled with plaque radiotherapy. Of the 25 recurrent tumors after CRD and EBRT, 100% were controlled with plaque radiotherapy. Of the 3 failures after plaque radiotherapy, the median time to failure (tumor recurrence) was 4 months and all recurrences were detected within 1 year. There were no identifiable factors predictive of plaque radiotherapy failure. Using Kaplan-Meier analysis, radiation complications at 5 years included proliferative retinopathy (19%), nonproliferative maculopathy (24%), papillopathy (16%), transient mild vitreous hemorrhage (54%), cataract (43%), iris neovascularization (NVI; 8%), and glaucoma (4%). Nonresolving vitreous hemorrhage and scleral necrosis did not occur. Radiation complications showed minimal change at 10 and 15 years of follow-up. CONCLUSIONS: Iodine 125 plaque radiotherapy offers 95% tumor control for selected retinoblastomas that fail CRD. Complications such as radiation retinopathy and mild vitreous hemorrhage should be anticipated, depending on the location, size, and extent of the tumor.

The International Classification of Retinoblastoma predicts chemoreduction success.

PURPOSE: To evaluate the reliability of the International Classification of Retinoblastoma (ICRB) for predicting treatment success with chemoreduction (CRD). DESIGN: Noncomparative interventional case series. PARTICIPANTS: Two hundred forty-nine consecutive eyes. METHODS: All eyes were treated with CRD and were classified according to the ICRB: group A included those eyes with retinoblastoma 3 mm, macular location, or minor subretinal fluid; group C included those eyes with retinoblastoma with localized seeds; group D included those eyes with retinoblastoma with diffuse seeds; group E included those eyes with massive retinoblastoma necessitating enucleation. The CRD regimen included vincristine, etoposide, and carboplatin for 6 cycles plus local consolidation with thermotherapy or cryotherapy. MAIN OUTCOME MEASURE: Chemoreduction success, defined as avoidance of external beam radiotherapy or enucleation. RESULTS: Of the 249 eyes, 23 (9%) were in group A, 96 (39%) were in group B, 21 (8%) were in group C, and 109 (44%) were in group D. In this series, group E eyes were managed with enucleation. Treatment success was achieved in 100% of group A, 93% of group B, 90% of group C, and 47% of group D eyes. CONCLUSIONS: The ICRB can be of assistance in predicting CRD success for retinoblastoma. Additional treatment methods are necessary to salvage more group D eyes.