Uveal Melanoma Treated With Iodine-125 Episcleral Plaque: An Analysis of Dose on Disease Control and Visual Outcomes

In the treatment of uveal melanomas, the optimal prescribed dose to maximize disease control, but minimize radiation-related complications is unknown. Historically our institution has treated uveal melanomas to doses less than 85 Gy to the tumor apex even if the apex was less than 5mm in height. Here, we investigate how tumor control and visual outcomes are affected by the radiation dose at the tumor apex

White paper on ophthalmic imaging for choroidal nevus identification and transformation into Melanoma

Purpose: To discuss the evolution of noninvasive diagnostic methods in the identification of choroidal nevus and determination of risk factors for malignant transformation as well as introduce the novel role that artificial intelligence (AI) can play in the diagnostic process. Methods: White paper. Results: Longstanding diagnostic methods to stratify benign choroidal nevus from choroidal melanoma and to further determine the risk for nevus transformation into melanoma have been dependent on recognition of key clinical features by ophthalmic examination. These risk factors have been derived from multiple large cohort research studies over the past several decades and have garnered widespread use throughout the world. More recent publications have applied ocular diagnostic testing (fundus photog-raphy, ultrasound examination, autofluorescence, and optical coherence tomography) to identify risk factors for the malignant transformation of choroidal nevus based on multimodal imaging features. The widespread usage of ophthalmic imaging systems to identify and follow choroidal nevus, in conjunction with the characterization of malignant transformation risk factors via diagnostic imaging, presents a novel path to apply AI. Conclusions: AI applied to existing ophthalmic imaging systems could be used for both identification of choroidal nevus and as a tool to aid in earlier detection of transformation to malignant melanoma. Translational Relevance: Advances in AI models applied to ophthalmic imaging systems have the potential to improve patient care, because earlier detection and treatment of melanoma has been proven to improve long-term clinical outcomes

Global Retinoblastoma Presentation and Analysis by National Income Level.

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

The global retinoblastoma outcome study : a prospective, cluster-based analysis of 4064 patients from 149 countries

DATA SHARING : The study data will become available online once all analyses are complete.BACKGROUND : Retinoblastoma is the most common intraocular cancer worldwide. There is some evidence to suggest that major differences exist in treatment outcomes for children with retinoblastoma from different regions, but these differences have not been assessed on a global scale. We aimed to report 3-year outcomes for children with retinoblastoma globally and to investigate factors associated with survival. METHODS : We did a prospective cluster-based analysis of treatment-naive patients with retinoblastoma who were diagnosed between Jan 1, 2017, and Dec 31, 2017, then treated and followed up for 3 years. Patients were recruited from 260 specialised treatment centres worldwide. Data were obtained from participating centres on primary and additional treatments, duration of follow-up, metastasis, eye globe salvage, and survival outcome. We analysed time to death and time to enucleation with Cox regression models. FINDINGS : The cohort included 4064 children from 149 countries. The median age at diagnosis was 23·2 months (IQR 11·0–36·5). Extraocular tumour spread (cT4 of the cTNMH classification) at diagnosis was reported in five (0·8%) of 636 children from high-income countries, 55 (5·4%) of 1027 children from upper-middle-income countries, 342 (19·7%) of 1738 children from lower-middle-income countries, and 196 (42·9%) of 457 children from low-income countries. Enucleation surgery was available for all children and intravenous chemotherapy was available for 4014 (98·8%) of 4064 children. The 3-year survival rate was 99·5% (95% CI 98·8–100·0) for children from high-income countries, 91·2% (89·5–93·0) for children from upper-middle-income countries, 80·3% (78·3–82·3) for children from lower-middle-income countries, and 57·3% (52·1-63·0) for children from low-income countries. On analysis, independent factors for worse survival were residence in low-income countries compared to high-income countries (hazard ratio 16·67; 95% CI 4·76–50·00), cT4 advanced tumour compared to cT1 (8·98; 4·44–18·18), and older age at diagnosis in children up to 3 years (1·38 per year; 1·23–1·56). For children aged 3–7 years, the mortality risk decreased slightly (p=0·0104 for the change in slope). INTERPRETATION : This study, estimated to include approximately half of all new retinoblastoma cases worldwide in 2017, shows profound inequity in survival of children depending on the national income level of their country of residence. In high-income countries, death from retinoblastoma is rare, whereas in low-income countries estimated 3-year survival is just over 50%. Although essential treatments are available in nearly all countries, early diagnosis and treatment in low-income countries are key to improving survival outcomes.The Queen Elizabeth Diamond Jubilee Trust and the Wellcome Trust.https://www.thelancet.com/journals/langlo/homeam2023Paediatrics and Child Healt

Update in Molecular Testing for Intraocular Lymphoma

The diagnosis of primary vitreoretinal lymphoma and central nervous system lymphoma is challenging. In cases with intraocular involvement, vitreous biopsy plays a pivotal role. Several diagnostic tests are employed to confirm a diagnosis and include cytologic evaluation, immunohistochemistry, flow cytometry, and cytokine analysis. The limitations of these conventional diagnostic tests stem from the often paucicellular nature of vitreous biopsy specimens and the fragility of malignant cells ex vivo. Several emerging molecular techniques show promise in improving the diagnostic yield of intraocular biopsy, possibly enabling more accurate and timely diagnoses. This article will review existing diagnostic modalities for intraocular lymphoma, with an emphasis on currently available molecular tests

Single-Blind and Double-Blind Peer Review: Effects on National Representation

To assess whether the type of peer-review (single-blinded vs double-blinded) has an impact on nationality representation in journals. A cross-sectional study analyzing the top 10 nationalities contributing to the number of articles across 16 ophthalmology journals. There was no difference in the percentage of articles published from the journal's country of origin between the top single-blind journals and double-blind journals (SB = 42.0%, DB = 26.6%, p = .49), but there was a significant difference between the percentage of articles from the US (SB = 48.0%, DB = 22.8%, p = .02). However, there was no difference for both country of origin (SB = 38.0%, DB = 26.6%, p = .43) and articles from the US (SB = 35.0%, DB = 22.8%, p = .21) when assessing the top eight double-blind journals matched with single-blind journals of a similar impact factor. The US (n = 16, 100%) and England (n = 16, 100%) most commonly made the top 10 lists for article contribution. This held true even for journals established outside the United States (US=11/12, England = 11/12). There was no significant difference in country-of-origin representation between single-blind journals and double-blind journals. However, higher income countries contributed most often to the journals studied even among journals based outside the US

Association between Tumor Regression Rate and Gene Expression Profile after Iodine 125 Plaque Radiotherapy for Uveal Melanoma

Gene expression profile (GEP) testing segregates uveal melanoma (UM) into 2 main prognostic classes. It is unknown if a greater tumor regression response after iodine 125 (I ) brachytherapy correlates with class 2 GEP status. The purpose of this study was to determine whether there is a significant relationship between the rate of UM height regression and GEP classification testing after I plaque brachytherapy. Multicenter, retrospective cohort study. Adult UM patients treated with I plaque brachytherapy who had concurrent tumor biopsy at the time of surgery with a GEP test result from January 1, 2010 through June 30, 2014. Baseline clinical data and GEP class assignments were obtained. The ultrasonographic tumor height was recorded at baseline and at 3, 6, 9, and 12 months and at the most recent final follow-up visits. Subanalysis of paired cases based on pretreatment ultrasound height was performed. Statistical analysis was performed using Wilcoxon rank-sum tests, the Fisher exact test, and Kaplan-Meier analysis. Percentage change in tumor height from baseline. A total of 353 patients were included in the study. Median follow-up was 2.1 years (range, 0.5-5.3 years). Gene expression profile status was class 1 in 247 tumors (70%) and class 2 in 106 tumors (30%). Increased patient age, larger tumor dimensions, and greater tumor thickness were associated with class 2 GEP status (P = 0.006, P < 0.001, and P < 0.001, respectively). The percentage reduction in tumor height from baseline was significantly greater in class 1 than class 2 tumors at 3 months (17.5% vs. 11.8%; P = 0.007) and 6 months (26.8% vs. 17.1%; P = 0.007), respectively, but there was no significant difference in reduction between class 1 and 2 tumors at 9 months (P = 0.26) and 12 months (P = 0.57) after treatment. Class 1A and 1B tumors showed similar reduction compared with class 2 tumors (P < 0.05). Class 1 UM tumors tend to regress more rapidly than class 2 tumors in the first 6 months after plaque radiotherapy. Class 1A and 1B tumors regress at similar rates after plaque radiotherapy

Endoscopic enucleation and clinicopathologic correlation of a small choroidal melanoma hiding massive extrascleral extension

Purpose: To report the unusual case of a previously stable choroidal nevus, closely followed for over 15 years, which underwent malignant transformation into small choroidal melanoma with massive extrascleral extension. Observations: A 67-year-old Caucasian female was referred to the Stanford Ocular Oncology Service with concern for malignant transformation of a previously stable choroidal nevus in her left eye. Her funduscopic examination demonstrated a dome-shaped choroidal lesion with overlying associated lipofuscin and subretinal fluid, consistent with a diagnosis of small choroidal melanoma. By B-scan ultrasonography, the lesion measured 8.0 × 6.0 mm in base and 2.1 mm in thickness. B-scan ultrasonography also disclosed an associated retroscleral mass, which appeared contiguous with the intraocular melanoma and was confirmed on subsequent orbital magnetic resonance imaging. A decision was made to proceed with enucleation. Under direct endoscopic visualization, the globe and extrascleral mass were fully isolated, mobilized, and removed in toto. At 24 months post-enucleation, the patient remains disease-free without evidence of systemic metastasis or local recurrence. Conclusions/importance: This case describes a small choroidal melanoma hiding massive extrascleral extension, underscoring the value of B-scan ultrasonography. This case also describes the unique management of choroidal melanoma with extrascleral extension using endoscopic enucleation. Performing enucleation under direct endoscopic visualization ensures complete resection and prevents inadvertent transection of the extrascleral component