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.

Clinical outcomes of hypofractionated radiation therapy for choroidal metastases: Symptom palliation, tumor control, and survival.

PURPOSE: External beam radiation therapy (RT) is an effective palliative treatment for patients with choroidal metastases and is aimed at preserving vision and obtaining local tumor control. Delivery of 30 to 40 Gy in 2-Gy daily fractions is a standard approach at many centers. This study reports the outcomes of a hypofractionated schedule of 20 Gy in 5 fractions in this palliative setting. METHODS AND MATERIALS: We conducted a retrospective review of patients who were treated with RT (20 Gy in 5 fractions) for choroidal metastases between January 1999 and November 2012. The primary outcome measures were change in visual acuity and tumor response. Secondary outcomes included toxicities of RT, tumor control, and overall survival (OS) from diagnosis of choroidal metastases. Univariate and multivariable Cox regression modeling was used to investigate the predictors for OS. RESULTS: Fifty-five patients with 71 affected eyes were included. Decreased vision was the presenting symptom in 43 eyes (61%). Visual acuity improved from a median of 20/70 at baseline to 20/40 at last follow-up and remained stable or improved in 56 eyes (80%). Tumor regression was observed in 64 eyes (91%) with complete response in 47 eyes (67%). Local progression occurred in 4 eyes (6%). The median survival after diagnosis of choroidal metastases was 13 months. No acute complications were observed in 49 patients (89%). Mild acute toxicities included transitory dryness in 5 patients and episcleritis in 1 patient. Cataracts, retinopathy, optic neuropathy, pigmentary maculopathy, and neovascular glaucoma developed in 4 eyes (6%), 1 eye, 7 eyes (10%), 5 eyes (7%), and 1 eye, respectively. No variables were statistically significantly associated with OS. CONCLUSIONS: A short fractionation schedule of 20 Gy in 5 fractions is a well-tolerated treatment that effectively preserves vision and gains local tumor control for many patients with choroidal metastases. This hypofractionated approach would help reduce the burden of a longer treatment course in this palliative patient population.

Bilateral multifocal choroidal melanosis: a report of two cases.

Flat choroidal pigmented lesions have few differential diagnoses but encompass a wide range of clinical presentations. The authors report two cases of bilateral multifocal choroidal hyper-pigmented patches discovered in asymptomatic patients. Fluorescein angiography showed a normal pattern without blockage in the hyperpigmented areas with an otherwise normal choroidal vascular architecture. Optical coherence tomography with enhanced depth imaging demonstrated normal choroidal thickness and structure in the hyperpigmented areas. These cases may represent an atypical presentation of previously described bilateral isolated choroidal melanocytosis or a different clinical entity. Histopathological evidence and longer follow-up of these patients and patients with isolated choroidal melanocytosis may elucidate the best descriptive term for this unusual condition.

Ultrasound biomicroscopy of the ciliary body in ocular/oculodermal melanocytosis.

PURPOSE: To describe the ultrasound biomicroscopy (UBM) findings of the ciliary body in patients with ocular/oculodermal melanocytosis. DESIGN: Retrospective observational case series study. METHODS: A retrospective chart and imaging database review was conducted for patients with unilateral ocular/oculodermal melanocytosis who underwent UBM examination at the Ocular Oncology Clinic of Princess Margaret Hospital. Radial images of the ciliary body at the 3-, 6-, 9-, and 12-o'clock positions were obtained in both eyes. UBM characteristics included ciliary body thickness and reflectivity. The eye with ocular/oculodermal melanocytosis was compared with the contralateral unaffected eye as a control. Statistical significance was analyzed with Student t test. RESULTS: Twelve patients were included. All patients showed unilateral diffuse pigmentation involving episclera and anterior chamber angle. The iris showed diffuse pigmentation in 10 cases and sectorial in 2. Mean ciliary body thickness of the affected eyes was 0.581 ± 0.058 mm (range 0.489-0.744) compared with 0.475 ± 0.048 mm (range 0.406-0.622) in the contralateral eye, which was found to be a statistically significant difference (P < .001). The affected ciliary body showed hyperreflectivity when compared with the unaffected eye. All affected eyes were graded as medium to high reflectivity compared with the unaffected eyes that showed a medium to medium/low reflectivity. CONCLUSION: Ciliary body involvement in ocular/oculodermal melanocytosis presents as increased thickness and higher ultrasound reflectivity on UBM when compared with the unaffected eye. UBM is helpful in imaging clinically undetectable areas of melanocytosis involving the ciliary body.

Presumed idiopathic central serous chorioretinopathy in a 12-year-old girl.

Idiopathic central serous chorioretinopathy (CSC) typically affects middle-aged males. To date, only one case of idiopathic CSC in a prepubertal subject has been reported. Atypical idiopathic CSC presentation may be challenging to diagnose. Exclusion of secondary causes of serous retinal detachment (SRD) is warranted. We describe the atypical case of a 12-year-old female with a circumscribed SRD that resolved spontaneously and with fluorescein angiography (FA) findings that were compatible with idiopathic CSC. Optical coherence tomography (OCT) and systemic assessment were performed to exclude other etiologies. FA demonstrated multiple focal leaks in early phases, with subretinal leakage and pooling in late phases. OCT showed a localized circumscribed retinal detachment. Complete blood count was within normal limits. Serum cortisol was normal (22.1 µg/dl) and mean arterial blood pressure was 100/60 mm Hg, thereby excluding secondary causes of CSC. This is the second reported case of idiopathic CSC in a prepubertal female and the first one documented by FA and OCT, as well as other studies to exclude secondary causes. Albeit rare, idiopathic CSC should be considered in the differential diagnosis of SRD in this (prepubertal) age group, after excluding secondary ocular or systemic etiologies.

Ocular toxicity of targeted therapies.

Molecularly targeted agents are commonly used in oncology practice, and many new targeted agents are currently being tested in clinical trials. Although these agents are thought to be more specific and less toxic then traditional cytotoxic chemotherapy, they are associated with a variety of toxicities, including ocular toxicity. Many of the molecules targeted by anticancer agents are also expressed in ocular tissues. We reviewed the literature for described ocular toxicities associated with both approved and investigational molecularly targeted agents. Ocular toxicity has been described with numerous approved targeted agents and also seems to be associated with several classes of agents currently being tested in early-phase clinical trials. We discuss the proposed pathogenesis, monitoring guidelines, and management recommendations. It is important for oncologists to be aware of the potential for ocular toxicity, with prompt recognition of symptoms that require referral to an ophthalmologist. Ongoing collaboration between oncologists and ocular disease specialists is critical as the use of molecularly targeted agents continues to expand and novel targeted drug combinations are developed.