The Pediatric Choroidal and Ciliary Body Melanoma Study: A Survey by the European Ophthalmic Oncology Group.

PURPOSE: To collect comprehensive data on choroidal and ciliary body melanoma (CCBM) in children and to validate hypotheses regarding pediatric CCBM: children younger than 18 years, males, and those without ciliary body involvement (CBI) have more favorable survival prognosis than young adults 18 to 24 years of age, females, and those with CBI. DESIGN: Retrospective, multicenter observational study. PARTICIPANTS: Two hundred ninety-nine patients from 24 ocular oncology centers, of whom 114 were children (median age, 15.1 years; range, 2.7-17.9 years) and 185 were young adults. METHODS: Data were entered through a secure website and were reviewed centrally. Survival was analyzed using Kaplan-Meier analysis and Cox proportional hazards regression. MAIN OUTCOME MEASURES: Proportion of females, tumor-node-metastasis (TNM) stage, cell type, and melanoma-related mortality. RESULTS: Cumulative frequency of having CCBM diagnosed increased steadily by 0.8% per year of age between 5 and 10 years of age and, after a 6-year transition period, by 8.8% per year from age 17 years onward. Of children and young adults, 57% and 63% were female, respectively, which exceeded the expected 51% among young adults. Cell type, known for 35% of tumors, and TNM stage (I in 22% and 21%, II in 49% and 52%, III in 30% and 28%, respectively) were comparable for children and young adults. Melanoma-related survival was 97% and 90% at 5 years and 92% and 80% at 10 years for children compared with young adults, respectively (P = 0.013). Males tended to have a more favorable survival than females among children (100% vs. 85% at 10 years; P = 0.058). Increasing TNM stage was associated with poorer survival (stages I, II, and III: 100% vs. 86% vs. 76%, respectively; P = 0.0011). By multivariate analysis, being a young adult (adjusted hazard rate [HR], 2.57), a higher TNM stage (HR, 2.88 and 8.38 for stages II and III, respectively), and female gender (HR, 2.38) independently predicted less favorable survival. Ciliary body involvement and cell type were not associated with survival. CONCLUSIONS: This study confirms that children with CCBM have a more favorable survival than young adults 18 to 25 years of age, adjusting for TNM stage and gender. The association between gender and survival varies between age groups.

Proton beam therapy for presumed and confirmed iris melanomas: a review of 36 cases.

BACKGROUND: To report the clinical features and outcomes of iris melanomas treated by proton beam therapy. MATERIALS AND METHODS: A retrospective study was conducted at the Croix-Rousse University Hospital of Lyon, Department of Ophthalmology, in 36 patients treated by proton beam therapy for presumed (n = 29) and confirmed (n = 7) iris melanomas between July 1997 and October 2010. Ciliary body melanomas with iris involvement were excluded. The patients' mean age was 54.4 years (range, 22-82 years). The average tumor diameter was 3.8 mm (range, 2.5-8.0). The iridocorneal angle was invaded by the tumor in 47% of cases (n = 17), the ciliary body in 17% of cases (n = 6), and the sclera in 3% (n = 1). Raised intraocular pressure was present before treatment in 11.1 % of cases (n = 4). Tumor biopsy was performed in 19% of cases (n = 7). Four patients had undergone an initial incomplete surgical excision of tumor before radiotherapy. Surgical preparation of the eye with tantalum ring positioning had been performed in all cases 3-4 weeks before irradiation. The prescribed dose was 60 Cobalt Gray Equivalent (CGE) of proton beam radiotherapy delivered in four fractions on four consecutive days. RESULTS: The median follow-up was 50 months (mean 60.5, range 15-136). One patient (2.7%) was lost to follow-up. None of the patients showed tumor progression, local recurrence, or metastasis. None of the patients required secondary enucleation. Cataract was developed in 62% of patients, glaucoma in two cases (6%) after irradiation, and hyphema with the aggravation of pre-existing glaucoma in one patient. No patients developed neovascular glaucoma. CONCLUSIONS: Proton beam therapy appears to be the treatment of choice for the conservative treatment of iris melanomas with excellent tumor control and an acceptable rate of complications. Longer follow-up studies on a larger series is necessary to consolidate these results.

Comparison of central macular thickness measured by three OCT models and study of interoperator variability.

PURPOSE: To compare central macular thickness (CMT) measurement on healthy patient using 3 different OCT devices by two operators. METHODS: Prospective, monocentricstudy. Right eye's central macular thickness (CMT) of 30 healthy patients has been measured three times using a time-domain (TD) OCT (Stratus OCT, Carl Zeiss Meditec, Dublin, Ca) and two spectral domain (SD) OCTs (Cirrus HD-OCT, Carl ZeissMeditec, Dublin, Ca) and 3D-OCT 1000 (Topcon, Tokyo, Japan) by two operators. Six measurements were taken randomly for each patient the same day. RESULTS: No significant difference between measurements obtained by the two operators has been observed, whatever the studied OCT. P value was 0.164, 0.193, and 0.147 for Stratus OCT, Cirrus HD-OCT and 3D-OCT, respectively. Mean CMT significantly differed from instrument to instrument (P < 0.001) and was, respectively, 197 µm, 254 µm, and 236 µm using Stratus OCT, Cirrus HD-OCT, and 3D-OCT 1000. Using Cirrus OCT and 3D-OCT 1000, CMT was, respectively, 57 µm and 39 µm thicker than using Stratus OCT (P < 0.05). CONCLUSIONS: Whatever the OCT device, on healthy patients CMT was not operator dependent. CMT measurements obtained by SD-OCTs are greater than those obtained by TD-OCT. These data imply that the different OCT devices cannot be used interchangeably in clinical monitoring.

20-year assessment of metastatic latency and subsequent time to death after proton therapy for uveal melanomas.

The aim of this study was to evaluate metastatic latency and survival after the occurrence of metastases in patients with choroidal/ciliary body melanoma treated with proton therapy. This was a retrospective cohort study. All consecutive patients with choroidal/ciliary body melanoma treated with proton therapy between 1991 and 2010 were included. Overall survival, specific survival (SS), local recurrence-free interval, and metastasis-free interval (MFI) were calculated. There were 508 patients. The mean follow-up was 239.4 months. Overall survival and SS rates were 57.2 and 67.6% at 10 years. Pre-equatorial tumor location, advanced tumor stage, and initial exudative retinal detachment were associated independently with SS. Thirty-three percent of the patients (n = 169) had metastases. Local recurrence-free interval and MFI were 91.3 and 65.7% at 10 years, respectively. MFI was shorter in pre-equatorial, large tumors, and/or tumors with exudative retinal detachment. After the occurrence of metastases, the median survival time was 1.25 years and survival probabilities were 62.1% at 1 year, 26.0% at 2 years, and 6.0% at 5 years. Except for age, none of the baseline clinical factors was associated with survival after metastasis occurrence. SS after metastasis occurrence was longer for metastasis occurring more than 10 years after tumor diagnosis (P =0.010). Death after metastasis is independent of initial tumor characteristics. Small tumors still have a risk for metastases after 10 years. Thus, lifelong follow-up is necessary for uveal melanoma patients. Larger series of metastatic patients are needed to evaluate aggressive multimodal treatments of metastases. Death after metastasis is independent of the initial tumor characteristics. Small tumors contraintuitively have a long-life risk of metastases. MFI is associated independently with pre-equatorial location, tumor stage, and retinal detachment.

The Small Fatal Choroidal Melanoma Study. A Survey by the European Ophthalmic Oncology Group.

PURPOSE: To determine the size at which choroidal melanomas can metastasize and to report the characteristics of small fatal choroidal melanomas (SFCM). DESIGN: Retrospective case series. METHODS: Ten ocular oncology services submitted 45 patients with a choroidal melanoma 3 mm or less in thickness and 9 mm or less in largest basal diameter (LBD), when treated, who developed metastases. RESULTS: Median tumor thickness was 2.4 mm (range, 1.0-3.0 mm) and LBD 7.3 mm (range, 3.0-9.0 mm). Of 14 (31%) tumors that were first observed, 12 grew a median of 0.5 mm (range, 0.1-1.2 mm) in thickness and 1.0 mm (range, 0-3.0 mm) in LBD within a median of 7 months; 3 were initially smaller than 3 mm in LBD. Number of risk factors for growth and metastasis was 0 for 4% of the tumors; 60% were over 2 mm in thickness, 63% had subretinal fluid, 84% caused symptoms, 57% had orange pigment, and 92% were within 3 mm of the disc. Local recurrence occurred in 8 of 31 eyes (26%) treated conservatively. Median metastasis-free survival was 4.5 years (range, 0.8-15.7 years). Kaplan-Meier estimate of metastasis developing was 15% (95% confidence interval [CI], 7-26), 51% (95% CI, 36-64) and 85% (95% CI, 71-92) by 2, 5, and 10 years, respectively. By the time of analysis, 37 patients had died of metastasis after a median of 7 months. CONCLUSIONS: Choroidal melanomas less than 3.0 mm in LBD are highly unlikely to metastasize. Risk factors of an SFCM are similar to those for all choroidal melanomas of similar size.

Abnormal cellular reactivity to microbial antigens in patients with uveitis.

PURPOSE: The purpose of the present study was to evaluate the cellular response to microbial antigens in patients with idiopathic uveitis. METHODS: Blood lymphocytes from 31 patients with uveitis and 24 healthy controls were cultivated with microbial antigens and analyzed by flow cytometry after staining with monoclonal antibodies against CD3, CD4, and activation markers CD69 and CD25. RESULTS: Although no difference was noted in circulating lymphocytes, the activation of T cells, detected with CD69, was higher in 24-hour blood culture from uveitis patients with Candida albicans antigen (Ca-Ag) than from controls, especially in posterior uveitis and panuveitis. Moreover, late response, detected with CD25, to different microbial antigens was higher in patient with uveitis. CONCLUSIONS: Such results suggest the role of Ca-Ag and microbial antigens in the pathogenic mechanisms of idiopathic uveitis.

Ocular anomalies associated with interstitial deletion of chromosome 2q31: case report and review.

We describe a newborn girl with multiple malformations associated with an interstitial deletion of chromosome 2q (q24q32). Clinical findings included growth retardation, microcephaly, facial malformations, common atrioventricular canal, digital anomalies of both hands and feet, and ovarian hypoplasia. Bilateral ocular anomalies included down-slanting palpebral fissures, blepharophimosis, microphthalmia, uveal coloboma, and corneal opacity. Chromosomal segment 2q31 may play a major role in the development of the eye and its adnexa.

Intravitreal dexamethasone implant (Ozurdex®) for exudative retinal detachment after proton beam therapy for choroidal melanoma.

PURPOSE: To evaluate the efficacy and safety of intravitreal 0.7-mg dexamethasone implant (DEX-I) (Ozurdex®) in the treatment of extensive exudative retinal detachment (RD) associated with uveal melanoma treated using proton beam therapy (PBT). METHODS: Data from 10 patients with exudative RD after PBT treated with intravitreal injection of 0.7-mg DEX-I were reviewed retrospectively. The main outcome measures were resolution of exudative RD, visual acuity, and safety profile. RESULTS: Mean age was 55.6 years (range 34-85). Mean time between PBT and DEX-I was 12.4 months (range 3-25). Mean follow-up was 9.9 months (range 4-15). Intravitreal Ozurdex® reduced exudative RD in 7 cases (70%) on average 3.1 months after injection with complete resolution of RD in 6 of these (60%). For half of the patients, their level of vision remained stable; the other half experienced a deterioration in visual acuity at the end of follow-up. No adverse effects were observed. CONCLUSIONS: In this small case series, treatment with intravitreal DEX-I reduced exudative RD in the majority of cases and had an acceptable safety profile.

Primary transpupillary thermotherapy for 18 small posterior pole uveal melanomas.

PURPOSE: To evaluate transpupillary thermotherapy (TTT) for the treatment of small uveal melanomas of the posterior pole. DESIGN: Prospective, nonrandomized interventional case series. METHODS: Eighteen patients underwent TTT for small uveal melanomas located in the posterior pole of the eyes. Tumors were between 2.5 and 4 mm in thickness. TTT was performed with a diode laser at 810 nm. Patients had between one and three TTT sessions, with an intensity adapted to the coloration of the fundus impact. Biomicroscopic examination, ultrasonographic measurements, and angiography were performed before and two months, four months, and six months after treatment, then regularly during follow-up. RESULTS: Eight of the 18 tumors regressed and 10 recurred. The one- and two-year metastasis-free survival rates calculated by the Kaplan-Meier method were, respectively, 61.11% to 44.44% (95% confidence interval). Recurrences were managed with enucleation (three patients), proton beam therapy (six), or additional thermotherapy (one). After treatment, visual acuity was maintained or improved for the eight patients with nonrecurrent tumors. Pathologic analysis of the three enucleated eyes revealed scleral invasion. CONCLUSIONS: Despite encouraging initial short-term results obtained with TTT for the management of small choroidal melanomas, the occurrence of severe complications, especially recurrences and insufficient local tumor control, should raise concern about indications for primary TTT given as isolated treatment for small melanomas of the posterior pole.

Visual Outcomes of Parapapillary Uveal Melanomas Following Proton Beam Therapy.

PURPOSE: In parapapillary melanoma patients, radiation-induced optic complications are frequent and visual acuity is often compromised. We investigated dose-effect relationships for the optic nerve with respect to visual acuity after proton therapy. METHODS AND MATERIALS: Of 5205 patients treated between 1991 and 2014, those treated using computed tomography (CT)-based planning to 52 Gy (prescribed dose, not accounting for relative biologic effectiveness correction of 1.1) in 4 fractions, with minimal 6-month follow-up and documented initial and last visual acuity, were included. Deterioration of ≥0.3 logMAR between initial and last visual acuity results was reported. RESULTS: A total of 865 consecutive patients were included. Median follow-up was 69 months, mean age was 61.7 years, tumor abutted the papilla in 35.1% of patients, and tumor-to-fovea distance was ≤3 mm in 74.2% of patients. Five-year relapse-free survival rate was 92.7%. Visual acuity was ≥20/200 in 72.6% of patients initially and 47.2% at last follow-up. A wedge filter was used in 47.8% of the patients, with a positive impact on vision and no impact on relapse. Glaucoma, radiation-induced optic neuropathy, maculopathy were reported in 17.9%, 47.5%, and 33.6% of patients, respectively. On multivariate analysis, age, diabetes, thickness, initial visual acuity and percentage of macula receiving 26 Gy were predictive of visual acuity. Furthermore, patients irradiated to ≥80% of their papilla had better visual acuity when limiting the 50% (30-Gy) and 20% (12-Gy) isodoses to ≤2 mm and 6 mm of optic nerve length, respectively. CONCLUSIONS: A personalized proton therapy plan with optic nerve and macular sparing can be used efficiently with good oncological and functional results in parapapillary melanoma patients.