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Retinoblastoma is the most frequent intraocular malignancy in children, originating from a maturing cone precursor in the developing retina. Little is known on the molecular basis underlying the biological and clinical behavior of this cancer. Here, using multi-omics data, we demonstrate the existence of two retinoblastoma subtypes. Subtype 1, of earlier onset, includes most of the heritable forms. It harbors few genetic alterations other than the initiating RB1 inactivation and corresponds to differentiated tumors expressing mature cone markers. By contrast, subtype 2 tumors harbor frequent recurrent genetic alterations including MYCN-amplification. They express markers of less differentiated cone together with neuronal/ganglion cell markers with marked inter- and intra-tumor heterogeneity. The cone dedifferentiation in subtype 2 is associated with stemness features including low immune and interferon response, E2F and MYC/MYCN activation and a higher propensity for metastasis. The recognition of these two subtypes, one maintaining a cone-differentiated state, and the other, more aggressive, associated with cone dedifferentiation and expression of neuronal markers, opens up important biological and clinical perspectives for retinoblastomas., (© 2021. The Author(s).)

There is increasing evidence of the survival benefit of treating uveal melanoma in an early stage, however it is important to discuss with the patient the associated risk of visual loss. We investigated visual outcomes for uveal melanomas staged T1 (T1UM) treated by proton beam radiotherapy (PBR) as a function of their distance to fovea-optic disc. This retrospective study included a cohort of 424 patients with T1UM treated with PBR between 1991 and 2010 with at least a 5-year follow-up. Visual acuity (VA) was analyzed for patients with posterior edge of tumor located at ≥3 mm (GSup3) or <3 mm (GInf3) from fovea-optic disc. The mean follow-up duration was 122 months, no tumor recurrence was observed. The mean baseline and final VA were 20/25 and 20/32 for GSup3 ( n = 75), and 20/40 and 20/80 for GInf3 ( n = 317) respectively. The frequency of a 20/200 or greater visual conservation was 93.2%(CI95%:87.7-99.1) and 60.1%(CI95%:54.9-65.9) for GSup3 and GInf3 respectively. This difference between groups was statistically significant ( p < 0.001). The risk factors for significant VA loss (less than 20/200) were GInf3 location ( p < 0.001), tumor touching optic disc ( p = 0.04), initial VA inferior to 20/40 ( p < 0.001), documented growth ( p = 0.002), and age greater than 60 years ( p < 0.001). In summary, PBR for T1UM yields excellent tumor control and good long-term visual outcomes for tumors located ≥3 mm from fovea-optic disc.

Patients with liver metastases of uveal melanoma (LMUM) die from their metastatic evolution within 2 years. We established a nomogram to choose a treatment adapted to life expectancy. From 2002 to 2013, we reviewed 224 patients with LMUM selected by liver MRI. A nomogram was developed based on a Cox model. The predictive performance of the model was assessed according to the C-statistic, Kaplan-Meier curve, and calibration plots. The median follow-up was 49.2 months (range, 0.6-70.9). The survival rates at 6, 12, and 24 months were 0.88 (0.95 CI [0.84-0.93]), 0.68 (0.95 CI [0.62-0.75]), and 0.26 (0.95 CI [0.21-0.33]), respectively. The four factors selected for the nomogram with a worse prognosis were: A disease-free interval between the UM and LMUM groups of less than 6 months (HR = 3.39; 0.95 CI [1.90-6.05]), more than 10 LMUM (HR = 3.95; 0.95 CI [1.97-4.43]), a maximum LMUM of more than 1200 mm2 (HR = 2.47; 0.95 CI [1.53-3.98]), and a lactate dehydrogenase (LDH) value greater than 1.5 (HR = 3.72; 0.95 CI [2.30-6.00]). The model achieved relatively good discrimination and calibration (C-statistic 0.71). This nomogram could be useful for decision-making and risk stratification for therapeutic options.

Background: To evaluate the efficacy of bevacizumab on reduction of the enucleation rate and control of intraocular pressure (IOP) in neovascular glaucoma (NVG)-complicating proton beam therapy for UM and to identify the determinants of the efficacy of bevacizumab., Methods: Retrospective comparative study of patients with rubeosis following proton therapy for uveal melanoma. Patients were divided into two groups: a bevacizumab group and a control group which comprised two subgroups: panretinal photocoagulation (PRP)/cryotherapy and observation subgroups. Bevacizumab was administered by three intravitreal injections at 1-month intervals. A second series of injections was administered when necessary. Data concerning IOP and the secondary enucleation rate were collected and compared between the two groups. Univariate and multivariate analyses were performed to determine predictive factors of response to bevacizumab., Results: A total of 169 patients who developed rubeosis following proton therapy between 2006 and 2016 were included: 44 patients in the bevacizumab group and 125 in the control group (38 in the PRP/cryotherapy subgroup and 87 in the observation subgroup). The two groups presented the same baseline characteristics apart from hypertension, retro-equatorial site, and proximity of the optic disk, which were more frequent in the control group, while initial retinal detachment and larger tumor volume were more frequent in the bevacizumab group. After a mean follow-up of 31 months, IOP was less than 21 mmHg in 54.54% of patients after IVB versus 72.7% before treatment (p = 0.06). Statistical analysis did not reveal any statistically significant reduction of the enucleation rate in the bevacizumab group compared to the observational group, whereas the PRP/cryotherapy group showed better eye retention rate (p = 0.15). No enucleation was performed when IOP was < 21 mmHg before IVB. Multivariate analysis identified initial IOP < 21 mmHg and UM situated away from the macula as predictive factors of good response to bevacizumab., Conclusion: Despite the improvement of IOP level, intravitreal bevacizumab (IVB) did not reduce the overall enucleation rate in NVG following proton beam therapy. Nevertheless, this treatment was effective in the early phases of NVG or as preventive treatment. PRP remains a valid treatment for NVG.

Intra-arterial infusion of chemotherapy into the ophthalmic artery for treatment of retinoblastoma has been realized after catheterization of the internal carotid and temporary balloon occlusion beyond the orifice of the ophthalmic artery, or more recently after superselective canulation of the ophthalmic artery by a microcatheter. The superselective catheterization of the ophthalmic artery could be cumbersome because of the implantation of the ostium on the carotid siphon or because of the tortuosity of the carotid siphon. We report our experience of using a retrograde approach through the posterior communicating artery that allows a more direct angle of access to the origin of the ophthalmic artery.

Background: Uveal metastases (UM) are the most common intraocular malignancies and can be the first manifestation of a disseminated disease. The purpose of this study is to determine the frequency with which uveal metastasis results in a diagnosis of lung cancer, to describe the clinical characteristics of patients with lung cancer metastatic to the uvea, as well as diagnostic difficulties that may be encountered., Patients and Methods: We carried out a single-center retrospective study of the medical records of all patients who presented with a UM between 1999 and 2010 at the institut Curie in Paris. From these patients, we retrospectively studied UM secondary to lung cancer. A work-up including thoracic-abdominal-pelvic CT was performed for each patient in whom the primary source of choroidal metastasis was unknown., Results: Of 109 patients presenting with UM, 43 were diagnosed with primary lung cancer (39.4%). Of those 43 patients, the UM was observed prior to the lung cancer in 31 patients (72.1%). Demographic data included 61% male and 39% female, mean age 59.1 years (range: 31-78), and mean life expectancy after diagnosis of UM was 7.5 months (range: 0.7-29). Other metastatic sites were associated with UM in 90.7% of the patients. In all, 90.7% of the patients presented with blurred vision, and 25.6% with pain or inflammation. UM were located within the choroid for 39 patients (90.7%), the iris for three patients (7.3%) and the vitreous for one patient. Seventy percent of patients had a solitary lesion, 76.7% had unilateral involvement, and 23.3% of cases were bilateral. Mean thickness on B-scan ultrasonography was 3.61 mm (range: 1-8.5 mm). In all, 81.4% of UM were unpigmented, while 18.6% showed pigment mottling. In all, 20.9% of patients were referred with the diagnosis of choroidal melanoma from their regular ophthalmologist, and three of the 43 patients (6.9%) were initially misdiagnosed and treated for melanoma at Curie. Chest X-ray was unremarkable in 18.9% of patients., Conclusion: UM is often the first manifestation of disseminated disease and requires a search for the primary tumor, in particular lung cancer. Standard chest X-ray cannot rule out the diagnosis. Metastases may be solitary with heterogenous pigmentation, and the differential diagnosis from uveal melanoma may be difficult, requiring the expertise of a referral center., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Fluorine 18 deoxyglucose positron emission tomography ((18)FDG PET) is widely used in staging of non-Hodgkin's lymphomas (NHL), but very few studies have focused on its role in the initial staging of patients with ocular adnexal lymphoma (OAL). The aim of this study was therefore to evaluate the role of (18)FDG PET in the diagnosis of ophthalmologic lymphoma. A retrospective review of all imaging records, including computed tomography (CT), magnetic resonance imaging (MRI), and FDG PET, was performed. Forty-one OAL patients were included in the study. A pathologic review according to the World Health Organization classification showed 32 low-grade lymphoma patients (78%), including 26 mucosa-associated lymphoid tissue lymphomas (63%). Ophthalmologic sites were intra-orbital + lacrimal gland in 24 patients (59%), conjunctival in 13 patients (32%), multiple in 4 cases, and bilateral in 6 patients. (18)FDG PET was positive in orbital and conjunctival sites in 68 and 35% of cases, respectively. (18)FDG PET positivity was correlated with pathologic sites detected by MRI in 22/30 patients (73%); (18)FDG PET positivity was correlated with pathologic sites detected by CT in 25/34 patients (73%). This study shows that (18)FDG PET has a lower sensitivity than MRI to detect ophthalmologic lymphoma, particularly in non-conjunctival sites.

Unlabelled: Treatments for choroidal melanoma (CM) generate largely unknown consequences on the level of the quality of life (QoL) and psychological state. Prospective published work is relatively rare and their results are not consistent. The objective of this study is to describe the QoL and psychological state's evolution in patients treated by conservative treatment for CM., Population: Sixty-nine patients treated for CM by conservative treatment (proton beam irradiation or iodine plaques). QoL (EORTC-QLQ-C30 + QLQ-OPT-30), anxiety and depression (HADS, STAI-B-trait)., Data Collection: Prospective study comprising four evaluations T0: before the beginning of the treatment, T1: one month, T2: six month, T3: one year after the treatment. The preliminary results of the first two evaluations showed that the level of the QoL remained relatively good and stable with an exception for the social functioning, which decreased after the treatment. More than half of the patients had a moderated rate of anxiety before the beginning of the treatment, which decreased significantly a month later. The depressive symptoms were lower and remained stable one month after the treatment. These results confirmed the importance of exploration and screening the fear of cancer recurrence among choroidal melanoma patients.

Purpose: To evaluate the long-term efficacy and outcome of low-dose proton beam irradiation in the treatment of symptomatic circumscribed choroidal hemangioma., Patients and Methods: Retrospective review of 71 patients with symptomatic circumscribed choroidal hemangiomas treated by proton beam irradiation between September 1994 and October 2002 using a total dose of 20 Cobalt Gray Equivalent., Results: The median follow-up was 52 months (8-133 months). Retinal reattachment was obtained in all cases. Tumor thickness decreased in all cases and a completely flat scar was obtained in 65 patients (91.5%). Visual acuity was improved by two lines or more in 37 of the 71 patients (52%), and in 30 of the 40 patients (75%) treated within 6 months after onset of the first symptoms. The main radiation complications detected during follow-up were cataract (28%) and radiation-induced maculopathy (8%). None of the 71 patients developed eyelid sequelae or neovascular glaucoma., Conclusion: Proton beam irradiation with a total dose of 20 Cobalt Gray Equivalent appears to be a valid treatment for circumscribed choroidal hemangiomas, inducing definitive retinal reattachment and decreasing tumor thickness. However, delayed radiation-induced maculopathy may occur. A successful functional outcome is dependent on a short interval between onset of the first symptoms and initiation of therapy.

The recent literature shows that interest in ocular adnexal lymphomas and their biologic and clinical characteristics--along with their possible association with Chlamydia psittaci infection and therapeutic management with rituximab or anti-Chlamydia psittaci antibiotic therapy--is considerable. These new data have modified the previously reported features of this disease and have made an updated review of the literature necessary. The aims of this review are to present the current knowledge on the biology of these lymphomas, their clinical features and prognostic factors, and the panel of all available treatment options.