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Radiation retinopathy is a retinal microangiopathy, observed after irradiation of the eye. It can rarely lead to neovascular glaucoma and enucleation due to pain. It is due to a progressive retinal capillary then vascular occlusion. Total irradiation dose, dose fraction, and surface of the irradiated retina seem to be strong predictive factors for radiation retinopathy. Patients who underwent an irradiation near the eye (skull base tumors, nasal and paranasal tumors, or brain tumors) should be followed by periodic ophthalmologic examination to detect and treat when necessary the non perfusion areas. [Copyright &y& Elsevier]

Introduction: Intraocular localization of conjunctival squamous cell carcinoma (SCC) is due to scleral or corneal invasion. Herein, we describe the clinical and histopathological findings in four cases of SCC complicated by intraocular invasion, and we review cases reported in the literature and their management. We retrospectively collected and analyzed clinical characteristics, histopathology, management, and follow-up data from 4 patients with conjunctival SCC complicated by intraocular invasion. We reviewed the literature and summarized cases of intraocular invasion by conjunctival SCC reported over the last 30 years., Case Presentations: Two patients presented with intraocular invasion by conjunctival SCC at diagnosis. The two others developed intraocular invasion as recurrence of conjunctival SCC, previously treated with excisional biopsy and adjuvant radiotherapy. All 4 cases had a previous history of conjunctival surgery, but no history of intraocular surgery. Three patients were managed with modified enucleation, including one that required adjuvant orbital radiotherapy. One patient required orbital exenteration. Histopathology analysis showed a well-differentiated conjunctival SCC in all cases. None developed distant localization after at least 2.5-year follow-up., Discussion/conclusion: Intraocular invasion is a rare complication of conjunctival SCC. Appropriate treatment in a tertiary center and long-term follow-up are highly recommended., Competing Interests: The authors have no conflicts of interest to declare., (© 2023 S. Karger AG, Basel.)

Background: The travel distance from home to a treatment centre, which may impact the stage at diagnosis, has not been investigated for retinoblastoma, the most common childhood eye cancer. We aimed to investigate the travel burden and its impact on clinical presentation in a large sample of patients with retinoblastoma from Africa and Europe., Methods: A cross-sectional analysis including 518 treatment-naïve patients with retinoblastoma residing in 40 European countries and 1024 treatment-naïve patients with retinoblastoma residing in 43 African countries., Results: Capture rate was 42.2% of expected patients from Africa and 108.8% from Europe. African patients were older (95% CI -12.4 to -5.4, p<0.001), had fewer cases of familial retinoblastoma (95% CI 2.0 to 5.3, p<0.001) and presented with more advanced disease (95% CI 6.0 to 9.8, p<0.001); 43.4% and 15.4% of Africans had extraocular retinoblastoma and distant metastasis at the time of diagnosis, respectively, compared to 2.9% and 1.0% of the Europeans. To reach a retinoblastoma centre, European patients travelled 421.8 km compared to Africans who travelled 185.7 km (p<0.001). On regression analysis, lower-national income level, African residence and older age (p<0.001), but not travel distance (p=0.19), were risk factors for advanced disease., Conclusions: Fewer than half the expected number of patients with retinoblastoma presented to African referral centres in 2017, suggesting poor awareness or other barriers to access. Despite the relatively shorter distance travelled by African patients, they presented with later-stage disease. Health education about retinoblastoma is needed for carers and health workers in Africa in order to increase capture rate and promote early referral., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: The analysis of circulating tumor DNA (ctDNA), a fraction of total cell-free DNA (cfDNA), might be of special interest in retinoblastoma patients. Because the accessibility to tumor tissue is very limited in these patients, either for histopathological diagnosis of suspicious intraocular masses (biopsies are proscribed) or for somatic RB1 studies and genetic counseling (due to current successful conservative approaches), we aim to validate the detection of ctDNA in plasma of non-hereditary retinoblastoma patients by molecular analysis of RB1 gene., Experimental Design: In a cohort of 19 intraocular unilateral non-hereditary retinoblastoma patients for whom a plasma sample was available at diagnosis, we performed high-deep next-generation sequencing (NGS) of RB1 in cfDNA. Two different bioinformatics/statistics approaches were applied depending on whether the somatic RB1 status was available or not., Results: Median plasma sample volume was 600 μL [100-1000]; median cfDNA plasma concentration was 119 [38-1980] and 27 [11-653] ng/mL at diagnosis and after complete remission, respectively. In the subgroup of patients with known somatic RB1 alterations (n = 11), seven of nine somatic mutations were detected (median allele fraction: 6.7%). In patients without identified somatic RB1 alterations (n = 8), six candidate variants were identified for seven patients., Conclusions: Despite small tumor size, blood-ocular barrier, poor ctDNA blood release and limited plasma sample volumes, we confirm that it is possible to detect ctDNA with high-deep NGS in plasma from patients with intraocular non-hereditary retinoblastoma. This may aid in diagnosis of suspicious cases, family genetic counseling or follow-up of residual intraocular disease., Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale., Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis., Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017., Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis., Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68])., Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs.

Purpose: The Sturge-Weber Syndrome (SWS) is a phacomatosis which include facial nevus flammeus, glaucoma, diffuse choroidal hemangioma, and leptomeningeal hemangiomatosis. External beam radiotherapy (EBRT) using photons was used to treat retinal detachment. We investigate the anatomical and functional results in a long-term basis., Methods: Retrospective review of SWS patients treated by EBRT (20 Gy in 10 fractions) for an exudative diffuse choroidal hemangioma. Visual acuity, B-scan tumor thickness, size of retinal detachment, intra-ocular pressure, and hypotonic treatment were collected before EBRT, 1 year after, and at the latest news., Results: Twenty-five patients (26 eyes) were treated between 2001 and 2014. Retinal detachment including the macula was found among twenty-six eyes before treatment. The average follow-up time was 47 months. The mean tumor thickness was initially 4.5 mm, 2.8 mm at first year, and 2.7 mm at the last visit. The retina was reattached at the last visit for all eyes except two. The visual acuity was stable or better for 20 eyes (p = 0.02). Four patients developed mild cataract during the follow-up., Conclusion: EBRT using 20 Gy in 10 fractions is efficient, decreases tumor thickness, reattaches the retina, and stabilizes visual acuity. In the long term, retinal reattachment allows ocular conservation by preventing phthisis bulbi.

Retinoblastoma is a rare cancer in children, where in less than a century of dire mortality there has been a cure in industrialized countries. Unfortunately, mortality remains high in emerging countries. The evolution of treatment makes it possible to go further by preserving the eyeball but this must not be done at the cost of the reappearance of metastases. Herein we outline the evolution of treatment from the beginning of the 20th century until the last recent evolutions, trying to imagine what could be the future treatments. In this pathology, the ophthalmologist is a doctor who must cure his patient and enucleation is considered a failure. This situation should not lead to shizophrenic situations where to keep an eye one would take risks with the life of the child. New international classifications, international prospective multicentric studies, and the search for blood biomarkers that can predict the risk of micrometastases could allow for better stratification of patients., (Copyright 2017 Asia-Pacific Academy of Ophthalmology.)

Retinoblastoma is a non-hereditary as well as an inherited pediatric tumor of the developing retina resulting from the inactivation of both copies of the RB1 tumor suppressor gene. Familial retinoblastoma is a highly penetrant genetic disease that usually develops by carrying germline mutations that inactivate one allele of the RB1 gene, leading to multiple retinoblastomas. However, large and complete germline RB1 deletions are associated with low or no tumor risk for reasons that remain unknown. In this study, we define a minimal genomic region associated with this low penetrance. This region encompasses few genes including MED4 a subunit of the mediator complex. We further show that retinoblastoma RB1 -/- cells cannot survive in the absence of MED4, both in vitro and in orthotopic xenograft models in vivo, therefore identifying MED4 as a survival gene in retinoblastoma. We propose that the contiguous loss of the adjacent retinoblastoma gene, MED4, explains the low penetrance in patients with large deletions that include both RB1 and MED4. Our findings also point to another synthetic lethal target in tumors with inactivated RB1 and highlight the importance of collateral damage in carcinogenesis., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The mutagenic properties of ionizing radiation are well known, but the presence of specific mutations in human radiation-induced tumours is not established. We have studied a series of 36 secondary sarcomas arising in the irradiation field of a primary tumour following radiotherapy. The allelic status and the presence of mutations of the TP53 gene were investigated. The mutation pattern was compared with data from sporadic sarcomas recorded in the IARC TP53 somatic mutations database. A high proportion (58%) of the radiation-induced sarcomas exhibited a somatic inactivating mutation for one allele of TP53, systematically associated with a loss of the other allele. The high frequency (52%) of short deletions observed in the mutation pattern of radiation-induced sarcomas may be related to the induction of DNA breaks by ionizing radiation. The lack of hyper-reactivity of CpG dinucleotides and the presence of recurrent sites of mutation at codons 135 and 237 seem also to be specific for radiation tumorigenesis.