Outcome Measures of New Technologies in Uveal Melanoma: Review from the European Vision Institute Special Interest Focus Group Meeting.

Uveal Melanoma (UM) is the most common primary intra-ocular tumor in adults. New diagnostic procedures and basic science discoveries continue to change our patient management paradigms. A recent meeting of the European Vision Institute (EVI) special interest focus group was held on "Outcome Measures of New Technologies in Uveal Melanoma", addressing the latest advances in UM, starting with genetic developments, then moving on to imaging and treatment of the primary tumor, as well as to investigating the most recent developments in treating metastases, and eventually taking care of the patient's wellbeing. This review highlights the meeting's presentations in the context of the published literature.

Blue-Light Fundus Autofluorescence Imaging following Ruthenium-106 Brachytherapy for Choroidal Melanoma.

PURPOSE: To describe changes in blue-light fundus autofluorescence (FAF) and corresponding alterations in optical coherence tomography (OCT) within the irradiation field after ruthenium-106 brachytherapy (RBT) for choroidal melanoma. METHODS: Consecutive patients with choroidal melanoma were included in a retrospective case series. Patients were treated with RBT at a single institution. As part of their routine examination patients underwent multimodal imaging including ultrasonography, fundus photography, OCT, and FAF imaging (excitation = 488 nm). FAF images were analysed for changes within the irradiation field. RESULTS: 31 patients (mean age 65.7 years) were treated with RBT for unilateral choroidal melanoma. Mean tumour height before therapy was 2.7 mm (SD 1.0). Mean follow-up time was 23.3 months (SD 13.3). Main FAF characteristics attributable to RBT emerged as increased FAF with speckled decreased FAF (FAF mottling) within the irradiation field and a rim of increased FAF at its border. OCT scans demonstrated loss of the ellipsoid zone and the external limiting membrane, thinning of the neurosensory retina, and alterations of the retinal pigment epithelium like clumping, migration, and atrophy. CONCLUSIONS: FAF changes in the irradiation field after RBT of choroidal melanomas follow a characteristic pattern that correlates with distinct OCT alterations. FAF and OCT imaging give additional information to monitor effects of RBT and, therefore, complement multimodal imaging techniques after plaque therapy.

Fundus Autofluorescence Imaging in Patients with Choroidal Melanoma.

Choroidal melanocytic lesions require reliable and precise clinical examination and diagnosis to differentiate benign choroidal nevi from choroidal melanoma, as the latter may become life-threatening through metastatic disease. To come to an accurate diagnosis, as well as for monitoring, and to assess the efficacy of therapy, various imaging modalities may be used, one of which is non-invasive fundus autofluorescence (FAF) imaging using novel high-resolution digital imaging technology. FAF imaging is based on the visualization of intrinsic fluorophores in the ocular fundus. Lipofuscin and melanolipofuscin within the postmitotic retinal pigment epithelium (RPE) cells represent the major fluorophores that contribute to the FAF signal. In addition, the presence or loss of absorbing molecular constituents may have an impact on the FAF signal. A choroidal melanoma can cause secondary retinal and RPE alterations that affect the FAF signal (e.g., occurrence of orange pigment). Therefore, FAF imaging supports multimodal imaging and gives additional information over and above conventional imaging modalities regarding retinal metabolism and RPE health status. This article summarises the features of FAF imaging and the role of FAF imaging in the context of choroidal melanoma, both before and following therapeutic intervention.

Neoadjuvant proton beam irradiation followed by transscleral resection of uveal melanoma in 106 cases.

AIMS: To describe results after neoadjuvant proton beam irradiation followed by transscleral resection of large uveal melanoma. METHODS: Retrospective interventional case series, including 106 consecutive patients. Local tumour control, enucleation and metastasis development were assessed with survival curves. Predictors of local recurrence and metastasis were investigated with log-rank testing. RESULTS: Mean follow-up was 3.2 years. Local recurrence occurred in five cases with an estimated risk of 4.2% and 10.4% at 3 and 5 years after treatment, respectively. Enucleation was performed in 10 cases with an estimated risk of 9.2% and 18.4% at 3 and 5 years, respectively. Significant risk factors for local recurrence were not evident. Metastasis was estimated to occur in 28.4% at 3 years and 40.3% at 5 years, correlating with patient's age only (p=0.01). Seventy four patients (69.8%) underwent vitreoretinal surgery for complications after tumour resection. Median visual acuity (VA) was 20/50 at diagnosis and 20/400 in the third year after treatment. VA preservation of 20/200 or better was achieved in 33 patients (31.1%). CONCLUSION: Neoadjuvant proton beam irradiation may help to prevent local recurrence after transscleral resection. Additional vitreoretinal surgery was frequently needed in the presented series. The majority of patients avoided enucleation and functional blindness.

The Development of Orange Pigment Overlying Choroidal Metastasis.

AIMS: The aim of this study was to correlate the ophthalmoscopic and histopathological findings of orange pigment overlying a choroidal metastasis. METHODS: This is a single case report with clinical follow-up and histopathological examination. RESULTS: Histopathology revealed a choroidal metastasis with subretinal CD68-positive macrophages showing autofluorescent deposits in fluorescence microscopy. CONCLUSION: The development of orange pigment is not pathognomonic for choroidal melanoma but may be seen in other lesions such as carcinoma metastasis.

Proton beam radiotherapy of diffuse iris melanoma in 54 patients.

BACKGROUND: Treatment modalities in iris melanoma include excision, plaque radiotherapy, photon or proton beam therapy and enucleation. In extensive tumours and diffuse seeding, radiotherapy remains as an alternative to enucleation. METHODS: This study is a retrospective, consecutive, interventional, single-institutional case series. 54 patients with a diffuse and non-resectable iris melanoma diagnosed from September 1998 to June 2012 were included. A 68-megaelectron volt proton beam was used to treat the anterior segment with a total dose of 4×12.5 cobalt grey equivalent. The cases were evaluated for local tumour control, eye retention, functional outcome and local complications after treatment. RESULTS: During a mean follow-up of 62.7 months (median 54.8 months, range 5.5-159.6 months), local tumour control was achieved in 96.3% of the patients. Cataract and glaucoma were the main complications developing after irradiation in 42.6% and 55.6%, respectively. In 34 of 44 patients (77.3%) who underwent cataract removal, a visual acuity of 20/40 or better following surgery was preserved. Enucleation was performed in three patients. The reason was suspected tumour recurrence in one and glaucoma in two. Hepatic metastasis occurred in one patient. CONCLUSIONS: As an alternative to enucleation, whole anterior segment fractionated proton beam radiotherapy offered excellent local tumour control in diffuse iris melanoma. Given the limited alternatives, the rate of complications appears acceptable and visual function could be preserved in the majority of the patients during follow-up.

Proton beam therapy of parapapillary choroidal melanoma.

PURPOSE: To analyze the functional outcome with regard to the development of visual acuity and radiation-induced optic neuropathy of patients with parapapillary choroidal melanoma treated with proton beam therapy. DESIGN: Clinical case series, retrospective study. METHODS: We evaluated 147 consecutive patients with parapapillary choroidal melanoma who received proton beam therapy as primary tumor treatment at the Helmholtz Center in Berlin from 1998 to 2005. A cumulative dose of 60 Cobalt Gray Equivalents (CGE) was delivered to the tumor and the optic disc received a minimum of 50 CGE. Kaplan-Meier analysis was used to assess ocular outcome and survival rates. For trend analysis of functional development, Wilcoxon-Mann-Whitney U test was used to compare the medians of 2 groups and Kruskal-Wallis test was used in the case of more than 2 groups. RESULTS: The mean follow-up time was 6.5 years (range 0.3-11.7 years). The most common side effects were radiation-induced optic neuropathy, retinopathy, and cataract. The median visual acuity before and within the first year after therapy was 0.4 logMAR (20/50), lapsing to 1.3 logMAR (20/400) after 3 years and 1.4 logMAR (20/500) after 5 years. During follow-up, no light perception developed in 17 cases (11.6%), mostly attributed to radiation-induced retinopathy, optic neuropathy, and secondary glaucoma. Enucleation was carried out in 14 patients (9.5%) because of local recurrence or severe side effects. CONCLUSION: Radiation-induced optic neuropathy is an expected issue after proton beam therapy of parapapillary choroidal melanoma, and visual impairment is common during long-term follow-up, but some useful vision can be preserved in a considerable number of patients.