En Face Depth Resolved OCTA Monitoring of Macular Outer Retinal Deposits in a Case of Multifocal Choroiditis Mimicking Syphilitic Uveitis.

PURPOSE: Multifocal choroiditis (MFC) is a rare inflammatory condition characterized by retinal and choroidal lesions that may present similarly to ocular pathology of various etiologies. Here we present a case of MFC mimicking syphilitic uveitis with unique en face optical coherence tomography angiography (OCTA) imaging characteristics. METHODS: Case report. RESULTS: A 61-year-old woman presented with blurry vision, floaters and multiple whitish subretinal deposits on en face swept-source OCTA in the left eye. Fluorescent treponemal antibody test absorption was positive which led to the initial diagnosis of syphilitic uveitis and subsequent treatment with intravenous penicillin. During follow-up, OCTA of the left eye revealed the development of new choroidal neovascular membrane and new punched-out lesions in the posterior pole. The patient was eventually diagnosed with MFC and treated with aflibercept injections. CONCLUSIONS: Immune-mediated uveitis can simulate infectious and neoplastic uveitis. En face OCTA is unique imaging modality that allowed for the complete characterization and monitoring of the sub-macular deposits. This expands the clinical spectrum of multifocal choroiditis.

Peripheral Hemorrhagic Chorioretinopathy: Differentiating Features from Choroidal Melanoma.

Introduction: Peripheral exudative hemorrhagic chorioretinopathy (PEHCR) is one of the leading mimickers of choroidal melanoma because of overlapping features with choroidal melanoma that make the distinction between these two entities difficult. Methods: To identify nonoverlapping diagnostic features between PEHCR and choroidal melanoma, a retrospective study of 80 patients (80 eyes); 40 patients (40 eyes) with PEHCR; and 40 patients (40 eyes) with choroidal melanoma was conducted. Ophthalmoscopic and imaging features of PEHCR and choroidal melanoma were compared. Sensitivity and specificity for identifying PEHCR and choroidal melanoma were calculated. Youden's J statistic was assessed for each diagnostic feature. Results: The most frequent clinical features of PEHCR were presence of druse (100%), hemorrhagic PED (93%), dome-shaped mass (B-scan) (90%), and subretinal/intraretinal hemorrhage (78%). Statistical analysis confirmed high sensitivity of hemorrhagic PED (0.93; 95% CI 0.80-0.98) and high specificity of clot retraction cleft, presence of lipid exudation, and bilaterality (1.00; 95% CI 0.91-1.00) as diagnostic features of PEHCR. Statistical analysis revealed presence of subretinal fluid 0.80 (95% CI 0.54-0.91) was most sensitive and presence of orange pigment, mushroom shape on B-scan, ciliary body extension, and choroidal excavation were most specific (1.00; 95% CI 0.91-1.00) for choroidal melanoma. Nonoverlapping diagnostic features of PEHCR were hemorrhagic PED, clot retraction cleft, presence of lipid exudation, and bilaterality. All PEHCR patients (100%) had at least one of these nonoverlapping diagnostic features. Nonoverlapping diagnostic features of choroidal melanoma were the presence of orange pigment, choroidal excavation, mushroom-shaped mass, and ciliary body extension (the latter 3 detected on B-scan). Youden's J statistic was highest for hemorrhagic PED and lowest for dome-shape appearance on B-scan (0.075). Conclusion: PEHCR and choroidal melanoma can be differentiated by identifying diagnostic features that are exclusive to each entity. The presence of hemorrhagic PED strongly supports a diagnosis of PEHCR. B-scan ultrasonography is required to detect a mushroom-shaped mass, choroidal excavation, or ciliary body extension to exclude underlying choroidal melanoma.

Uveal Melanoma in BAP1 Tumor Predisposition Syndrome: Estimation of Risk.

PURPOSE: To estimate point prevalence of uveal melanoma in the patients with germline BAP1 pathogenic variant. DESIGN: Cohort study with risk assessment using Bayesian analysis. METHODS: The point prevalence estimate was obtained by Bayes's rule of reverse conditional probabilities. The probability of uveal melanoma given that BAP1 mutation exists was derived from the prevalence of uveal melanoma, prevalence of germline BAP1 pathogenic variants, and the probability of germline BAP1 pathogenic variant given that uveal melanoma is present. Confidence intervals (CIs) for each variable were calculated as the mean of Bernoulli random variables and for the risk estimate, by the delta method. The age at diagnosis and the gender of the uveal melanoma patients with BAP1 germline pathogenic variants obtained from previous publications or from authors' unpublished cohort was compared with those in the Surveillance, Epidemiology, and End Results (SEER) database. RESULTS: The point prevalence of uveal melanoma in patients with the germline BAP1 pathogenic variants in the US population was estimated to be 2.8% (95% CI, 0.88%-4.81%). In the SEER database, the median age at diagnosis of uveal melanomas was 63 (range 3-99 years) with a male-to-female ratio of 1.01:1. In comparison, uveal melanoma cases with BAP1 germline pathogenic variants from the US population (n = 27) had a median age at diagnosis of 50.5 years (range 16-71). CONCLUSIONS: Quantification of the risk of developing uveal melanoma can enhance counseling regarding surveillance in patients with germline BAP1 pathogenic variant.

An Online Application for Retinoblastoma Surveillance.

BACKGROUND: Retinoblastoma (RB) is a potentially heritable childhood cancer that is vision- and life-threatening. Assessing the risk of inheriting RB is important for structuring ophthalmic and genetic screening of family members. PURPOSE: To create a free online application that integrates phenotypic, genetic, and familial relationships with clinical best practice surveillance guidelines for families with RB. METHODS: The risk of germline RB1 gene mutation was assessed for first- and second-degree relatives of a proband under variable clinical scenarios, integrating age, phenotype, relationship data, and genotype (germline RB1 mutation status: detected, undetected, not tested). Based on the assessed risk of a germline RB1 mutation, recommendations regarding further genetic testing as well as ophthalmic surveillance were derived from consensus guidelines. RESULTS: The recommendations depend on the RB1 germline mutation status (detected, undetected, not tested), which were further subcategorized by the results of tumor phenotype, relationship to proband, age of the relative, and family structure. The online application is available at https://nakul-singh.shinyapps.io/RB_Screening_rec/. CONCLUSIONS: The assessed risk of germline RB1 mutation determines ophthalmic surveillance recommendations. The tool may have most value in regions where access to specialized care is limited.

Fine-needle aspiration biopsy for suspected uveal metastases.

OBJECTIVE: One indication of fine-needle aspiration biopsy (FNAB) is the diagnostic confirmatory of a clinical suspicion of uveal metastasis. We analyzed our experience in this clinical setting to assess the effectiveness of FNAB technique. DESIGN: Retrospective study. PARTICIPANTS: 28 patients (28 eyes) underwent FNAB biopsy. METHODS: Aspirates were performed using 25-gauge needle and were classified into the following categories: positive, atypical, negative, or nondiagnostic. The electronic medical records provided all clinical data. Subsequent clinical course was considered as the diagnostic standard. RESULTS: Subsequent clinical course was metastatic tumour in 19 cases (68%) and nonmetastatic tumour in other 9 cases, considered as the diagnostic standard. Cytological interpretations for metastases were positive in 19 cases (68%), atypical in 2 cases (7%), negative in 4 cases (14%), and nondiagnostic in 3 cases (11%). The metastasis-positive cases included 9 adenocarcinoma, 3 uveal lymphoma, 3 small cell carcinomas, 3 non-small cell carcinomas, and 1 metastatic paraganglioma. Both of the atypical cases were suggestive for non-Hodgkin lymphoma. The 4 negative cases for metastases included 2 true negative cases, and 2 false negative aspirates that subsequently proved to be metastatic adenocarcinoma. The 3 nondiagnostic cases included 1 schwannoma, 1 low-grade uveal non-Hodgkin lymphoma, and 1 metastatic adenocarcinoma. The overall sensitivity for FNAB was 87.5%, with a specificity of 100%. CONCLUSIONS: FNAB of suspected uveal metastases is a reliable diagnostic technique.

Diagnostic A-Scan of Choroidal Melanoma: Automated Quantification of Parameters.

AIM: To develop an automated algorithm to quantify ultrasonographic A-scan parameters of choroidal melanoma. METHODS: The study included 100 consecutive patients with a clinical diagnosis of choroidal melanoma. Ultrasonographic A-scans (8 MHz, 1,550 m/s, tissue sensitivity = 67 dB) were performed by standard techniques. We created and then utilized a MATLAB® script to generate four quantifiable A-scan parameters: (1) tumor height (mm), (2) the number of internal reflectivity peaks (numerical value), (3) median internal reflectivity (%), and (4) angle κ (°). RESULTS: There were small (≤2.5 mm, n = 32), medium (2.6-10.0 mm, n = 53), and large (> 10.0 mm, n = 14) tumors. The mean number of internal reflectivity peaks counted between the two tumor boundary spikes (surface and base) was 10.0 (σ = 8.7, range 1-37). The median value of the internal reflectivity peaks for all cases varied from 19.8 to 99.5 (mean = 68.3, σ = 20.5). A statistically significant correlation was observed between the tumor height categories and each of the three A-scan parameters: the number of internal reflectivity peaks (ρ = 0.90, p < 0.01), median internal reflectivity (ρ = -0.63, p < 0.01), and a positive angle κ (ρ = -0.32, p = 0.03). CONCLUSIONS: An automated algorithm can provide quantifiable A-scan parameters for choroidal melanoma.

Diagnostic A-Scan of Choroidal Tumors: Comparison of Quantified Parameters.

AIM: To compare quantified ultrasonographic A-scan parameters of common choroidal tumors. METHODS: Consecutive patients with a clinical diagnosis of choroidal melanoma (n = 100), choroidal nevus (n = 30), choroidal metastasis (n = 10), and circumscribed choroidal hemangioma (n = 10) were included in this study. Ultrasonographic A-scans (8 MHz, 1,550 m/s, tissue sensitivity = 67 dB) were performed by standard techniques. Using a custom made MATLAB® script, four quantifiable A-scan parameters: tumor height (mm), number of internal reflectivity peaks (numerical value), median internal reflectivity (%), and angle κ (°) were obtained for all (n = 150) tumors. RESULTS: The mean number of internal reflectivity peaks for choroidal nevus, choroidal metastasis, and circumscribed choroidal hemangioma was 3.1, 5.1, and 4.0, respectively. The median internal reflectivity for choroidal melanoma varied from 21.5 to 99.5% (mean = 76.4%). The median internal reflectivity was ≥65% in all choroidal nevus (100%), choroidal metastasis (100%), and circumscribed choroidal hemangioma (100%), and majority of the choroidal melanoma (78%). CONCLUSIONS: The quantified A-scan patterns of common choroidal tumors were significantly influenced by the tumor height. Other than median internal reflectivity of < 65%, which seems to distinguish choroidal melanoma from other tumors (choroidal nevus, choroidal metastasis, and circumscribed choroidal hemangioma), there were no specific diagnostic patterns.

Variability of Bad Prognosis in Uveal Melanoma.

TOPIC: Survival of patients with uveal melanoma classified to have a bad prognosis. CLINICAL RELEVANCE: To explore reasons for reported variability in survival of patients with uveal melanoma classified to have a bad prognosis. METHODS: We searched PUBMED, MEDLINE, and EMBASE for studies reporting survival data for uveal melanoma undergoing prognostic testing with chromosome 3 status by fluorescence in situ hybridization (FISH), comparative genomic hybridization (CGH), microsatellite analysis (MSA), multiplex ligation-dependent probe amplification (MLPA), single nucleotide polymorphism (SNP), gene expression profiling (GEP) class, and exon sequencing. Only studies reporting 1-year, 3-year, or 5-year survival were included in the study. RESULTS: The initial search resulted in 49 studies. Only 12 studies met inclusion criteria. Three studies reported survival data for FISH, 1 study reported survival data for CGH, 1 study reported survival data for MSA, 3 studies reported survival data for MLPA, 3 studies reported survival data for SNP, 3 studies reported survival data for GEP, and 2 studies reported survival data for a combination of tests. No studies reported survival data for exon sequencing. Six studies reported percent free of metastatic death, 2 studies reported metastasis-free survival (MFS), 2 studies reported overall survival (OS), and 2 studies reported probability of metastasis. Metastasis-free survival (5 years) for monosomy 3 by FISH was 40% to 60%, by MLPA was 30% to 40%, by SNP was 72%, and for GEP class 2 was not reported. Overall survival (5 years) for monosomy 3 and disomy 8 tumors by MLPA and GEP class 2 were not comparable (81% and 55%, respectively). CONCLUSIONS: Variability exists in reported survival for uveal melanoma with a bad prognosis. Several factors, including composition of study population (tumor size, exclusion of iris melanoma, duration of median follow-up), method of obtaining tumor sample, type of prognostic test, and use of variable outcome measures, can explain some of the observed differences in survival. Variations in determining the cause of death (metastatic or nonmetastatic) may be the major reason for the observed differences. Standardization of study methods and outcome measures will allow comparison of survival data derived from different prognostic tests.

The Amazon Ocular Oncology Center: The first three years / Centro de Oncologia Ocular do Amazonas: primeiros três anos

ABSTRACT Purpose: To evaluate the first three years of The Amazon Ocular Oncology Center, the first ocular cancer center in the North of Brazil. Methods: Here, we report patient information including patients' age, gender, diagnosis, treatment, and city of origin. Results: Two hundred and twenty-one patients were included on this study: 160 (72%) patients came from the city of Manaus, 52 (24%) from other cities in Amazonas, and 9 (4%) from other states. Of the 221 patients, 150 (68%) were afflicted with benign lesions and the remaining 71 (32%) had malignant lesions. Benign diagnosis included pterygium, chalazium, conjunctival nevus, and papilloma, cataract, and retinal detachment. Of the malignant cases, squamous cell carcinoma (SCC) of the conjunctiva was the most frequent with 43 cases (60%). Other diagnoses included choroidal melanoma (8 cases, 11%), retinoblastoma (7 cases, 9%), lymphomas (5 cases, 7%), basal cell carcinomas of the eyelid (4 cases, 5%), conjunctival melanoma (2 cases, 2%), and Kaposi sarcomas (1 case, 1%). Of the 43 patients with SCC, the mean age was 62 years old, and 30 (69%) were male; 29 patients (67%) were treated with an excisional biopsy, and 14 (33%) were treated with neoadjuvant topic chemotherapy, followed by surgery.

RESUMO Objetivo: Reportar sobre os primeiros três anos do Centro de Oncologia Ocular do Amazonas, primeiro centro de oncologia ocular na região Norte do Brasil. Métodos: Relatamos informações de diagnóstico, idade, sexo, tratamento e cidade de origem dos pacientes atendidos nos 3 primeiros anos. Resultados: Identificamos 221 pacientes, dos quais 160 (72%) eram da cidade de Manaus, 52 (24%) de outras cidades do Amazonas e 9 (4%) de outros estados. Dos 221 casos, 150 (68%) eram lesões benignas e 71 (32%) malignas. Lesões benignas incluíram pterígio, calázio, nevus e papiloma de conjuntiva, catarata e descolamento de retina. Das lesões malignas a mais comum foi o carcinoma escamoso de conjuntiva com 43 casos (60%). Outros diagnósticos incluíram melanoma de coróide (8 casos, 11%), retinoblastoma (7 casos, 9%), linfomas (5 casos, 7%), carcinoma da pálpebra (4 casos, 5%), melanoma da conjunctiva (2 casos, 2%) e sarcoma de Kaposi (1 caso, 1%). Dentre os CEC de conjuntiva, a idade media foi de 62 anos e 30 pacientes (69%) eram do sexo masculino. Vinte e nove casos (67%) foram tratados com biópsia excisional e 14 (33%) com quimioterapia tópica neoadjuvante seguida de cirurgia.

The Amazon Ocular Oncology Center: The first three years.

PURPOSE: To evaluate the first three years of The Amazon Ocular Oncology Center, the first ocular cancer center in the North of Brazil. METHODS: Here, we report patient information including patients' age, gender, diagnosis, treatment, and city of origin. RESULTS: Two hundred and twenty-one patients were included on this study: 160 (72%) patients came from the city of Manaus, 52 (24%) from other cities in Amazonas, and 9 (4%) from other states. Of the 221 patients, 150 (68%) were afflicted with benign lesions and the remaining 71 (32%) had malignant lesions. Benign diagnosis included pterygium, chalazium, conjunctival nevus, and papilloma, cataract, and retinal detachment. Of the malignant cases, squamous cell carcinoma (SCC) of the conjunctiva was the most frequent with 43 cases (60%). Other diagnoses included choroidal melanoma (8 cases, 11%), retinoblastoma (7 cases, 9%), lymphomas (5 cases, 7%), basal cell carcinomas of the eyelid (4 cases, 5%), conjunctival melanoma (2 cases, 2%), and Kaposi sarcomas (1 case, 1%). Of the 43 patients with SCC, the mean age was 62 years old, and 30 (69%) were male; 29 patients (67%) were treated with an excisional biopsy, and 14 (33%) were treated with neoadjuvant topic chemotherapy, followed by surgery.

Extranodal Marginal Zone Lymphoma of Ocular Adnexa: Outcomes following Radiation Therapy.

AIM: The aim of this study was to report outcomes following radiation therapy in patients with biopsy-proven extranodal marginal zone lymphoma of the ocular adnexa and uvea. METHODS: Records from a single institution were retrospectively reviewed from January 1997 to December 2015. The mean follow-up duration was 38 months (range 0-194). Radiation therapy was administered to 77 eyes (60 patients); 57 of the 77 eyes (74%) were treated with radiation only (range 20-36 Gy, median 15 fractions). Radiation cataract, radiation retinopathy, and optic neuropathy assessments were performed on all eyes treated with radiation. RESULTS: 100% of the 47 patients treated with radiation therapy only had local control with an average dose of 26.5 Gy (median 25.2 [range 20-36] Gy; 150-200 cGy per fraction). Four patients lost 2 lines or more of vision after radiation. The most common complication of radiation therapy was cataract formation/progression in 19 eyes (25%). Radiation retinopathy was observed only in 1 patient (1%). CONCLUSION: Our results confirm that radiation therapy (median 25 Gy) for extranodal marginal zone lymphoma of the ocular adnexa is associated with high local control and low risk of visually significant complications.

Iodine-125 Brachytherapy for Uveal Melanoma: A Systematic Review of Radiation Dose.

AIM: To investigate whether lower radiation doses may yield similar outcome measures to those from the COMS trial. METHODS: A literature review of English language articles was performed using the PubMed database of the U.S. National Library of Medicine and the Cochrane Central Register of Controlled Trials using the following keywords: uveal melanoma, choroidal melanoma, primary uveal malignant melanoma, iodine-125 brachytherapy, local recurrence, local treatment failure, and local tumor control. The relationships between study local recurrence rate and median dosage were tested by linear regression, with each study weighted by the number of patients included. RESULTS: Fifteen retrospective and prospective studies were selected for systematic review (2,662 patients). Ranges of reported mean or median radiation dose to tumor apex were 62.5-104.0 Gy. Local recurrence rates ranged from 0 to 24%. A 1.0-Gy increase in the average study dose was associated with a 0.14% decrease in local recurrence rate, which was not statistically significant (p value 0.336). CONCLUSION: The gold standard empirically derived 85.0-Gy radiation dose for the treatment of uveal melanoma could be tested in a randomized study.

Uveal Melanoma Regression after Brachytherapy: Relationship with Chromosome 3 Monosomy Status.

AIM: The objective was to evaluate the relationship between the regression rate of ciliary body melanoma and choroidal melanoma after brachytherapy and chromosome 3 monosomy status. METHODS: We conducted a prospective and consecutive case series of patients who underwent biopsy and brachytherapy for ciliary/choroidal melanoma. Tumor biopsy performed at the time of radiation plaque placement was analyzed with fluorescence in situ hybridization to determine the percentage of tumor cells with chromosome 3 monosomy. The regression rate was calculated as the percent change in tumor height at months 3, 6, and 12. The relationship between regression rate and tumor location, initial tumor height, and chromosome 3 monosomy (percentage) was assessed by univariate linear regression (R version 3.1.0). RESULTS: Of the 75 patients included in the study, 8 had ciliary body melanoma, and 67 were choroidal melanomas. The mean tumor height at the time of diagnosis was 5.2 mm (range: 1.90-13.00). The percentage composition of chromosome 3 monosomy ranged from 0-20% (n = 35) to 81-100% (n = 40). The regression of tumor height at months 3, 6, and 12 did not statistically correlate with tumor location (ciliary or choroidal), initial tumor height, or chromosome 3 monosomy (percentage). CONCLUSION: The regression rate of choroidal melanoma following brachytherapy did not correlate with chromosome 3 monosomy status.

Open Payments Database: Anti-Vascular Endothelial Growth Factor Agent Payments to Ophthalmologists.

PURPOSE: To analyze anti-vascular endothelial growth factor (anti-VEGF) agent-associated industry payments to ophthalmologists using the Centers for Medicare and Medicaid Services (CMS) Open Payments and Provider Utilization and Payment data. DESIGN: Retrospective database review using 2 national databases. METHODS: Payments from 2013 to 2014 were analyzed by anti-VEGF agent, payment category, and dollar amount. Ranibizumab and aflibercept usage was correlated by performing log-ratio analysis. RESULTS: A total of 3207 ophthalmologists received 13 449 payments totaling $4 454 325 associated with ranibizumab and aflibercept. As 7% of ophthalmologists received 90% of payments, the Gini index was 0.92, demonstrating unequal distribution of payments. Consulting fees and speaker fees were associated with highest payment amounts to fewest providers. For 2383 providers (74%), greater than 90% of the anti-VEGF payments were associated exclusively with either ranibizumab or aflibercept. A total of 1382 ophthalmologists were matched in both databases. Providers receiving >90% of payments from ranibizumab were more likely to use ranibizumab, and those receiving >90% of payments from aflibercept were more likely to use aflibercept over bevacizumab as compared to those who received no payments. CONCLUSIONS: The distribution of all anti-VEGF payments is unequal. Ophthalmologists who received aflibercept or ranibizumab payments were more likely to receive the majority of payments from one source or the other, but not both. Those who received anti-VEGF payments were more likely to use ranibizumab or aflibercept, as compared to off-label bevacizumab, than those who did not receive any payment.

Metrics for monitoring cancer inequities: residential segregation, the Index of Concentration at the Extremes (ICE), and breast cancer estrogen receptor status (USA, 1992-2012).

PURPOSE: To address the paucity of evidence on residential segregation and cancer, we explored their relationship using a new metric: the Index of Concentration at the Extremes (ICE). We focused on breast cancer estrogen receptor (ER) status, a biomarker associated with survival and, etiologically, with social and economic privilege. METHODS: We obtained data from the 13 registry group of US Surveillance, Epidemiology, and End Results (SEER) program for 1992-2012 on all women aged 25-84 who were diagnosed with primary invasive breast cancer (n = 516,382). We appended to each case's record her annual county median household income quintile and the quintile for her annual county value for ICE measures for income (≤20th vs. ≥80th household income quintile), race/ethnicity (black vs. white), and income plus race/ethnicity (low-income black vs. high-income white). The odds of being ER+ versus ER- were estimated in relation to the county-level income and ICE measures, adjusting for relevant covariates. RESULTS: Women in the most privileged versus deprived county quintile for household income and for all three ICE measures had a 1.1- to 1.3-fold increased odds (95 % confidence intervals excluding 1) of having an ER+ tumor. These results were robust to adjustment for age at diagnosis, cancer registry, tumor characteristics (tumor stage, size, histology, grade), and race/ethnicity. CONCLUSION: A focus on segregation offers news possibilities for understanding how inequitable group relations contribute to cancer inequities. The utility of employing the ICE for monitoring cancer inequities should be investigated in relation to other cancer outcomes.

Validation of the rapid test carestart(tm) G6PD among malaria vivax-infected subjects in the Brazilian Amazon

Abstract: INTRODUCTION: In the Brazilian Amazon, malaria infections are primarily caused by Plasmodium vivax. The only drug that kills the hypnozoite form of P. vivax is primaquine, thereby preventing relapse. However, treating glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals with primaquine can lead to severe hemolysis. G6PD deficiency (G6PDd) affects approximately 400 million people worldwide, most of whom live in malaria-endemic areas. Therefore, clinicians need tools that can easily and reliably identify individuals with G6PDd. This study estimated the accuracy of the Carestart(tm) G6PD rapid test (Access Bio) in the diagnosis of G6PDd in male participants with and without P. vivax acute malaria. METHODS: Male participants were recruited in Manaus. Malaria diagnosis was determined by thick blood smear. G6PD quantitative analysis was performed spectro photometrically at a wave length of 340nm. The Carestart(tm) G6PD test was performed using venous blood. Genotyping was performed for individuals whose samples had an enzyme activity less than 70% of the normal value. RESULTS: Six hundred and seventy-four male participants were included in this study, of whom 320 had a diagnosis of P. vivax malaria. In individuals with enzyme activity lower than 30% (n=13), the sensitivity, specificity, positive predictive value, and negative predictive value of the Carestart(tm) G6PD test were as follows: 61.5% (95%CI: 35.5%-82.3%), 98.3% (95%CI: 97.0%-99.1%), 42.1% (95%CI: 23.1%-63.7%), and 99.2% (95%CI: 98.2%-82.3%), 98.3% (95%CI: 97.0%-99.1%), 42.1% (95%CI: 23.1%-63.7%), and 99.2% (95%CI: 98.2%-99.7%), respectively. Increases in sensitivity were observed when increasing the cut-off value. CONCLUSIONS: Despite low sensitivity, Carestart(tm) G6PD remains a good alternative for rapid diagnosis of G6PDd in malaria-endemic regions.

Vision Loss Following Episcleral Brachytherapy for Uveal Melanoma: Development of a Vision Prognostication Tool.

IMPORTANCE: Vision loss following episcleral brachytherapy for uveal melanoma is difficult to predict for individual patients. OBJECTIVE: To generate a risk calculator for vision loss following episcleral brachytherapy for uveal melanoma. DESIGN, SETTING, AND PARTICIPANTS: A retrospective review of data was conducted at a multispecialty tertiary care center in Cleveland, Ohio. All patients with primary ciliary body or choroidal melanoma treated with iodine 125 or ruthenium 106 episcleral brachytherapy between January 1, 2004, and December 30, 2013, were included. Univariate and multivariable Cox proportional hazards were used to determine the influence of baseline patient factors on vision loss. Kaplan-Meier curves (log-rank analyses) were used to estimate freedom from vision loss. Bootstrap resampling was performed to bias correct this estimate. MAIN OUTCOMES AND MEASURES: Vision loss (to visual acuity [VA] worse than 20/50 and worse than 20/200). RESULTS: A total of 311 patients were included in the study, with a mean (SD) age of 62 (14.7) years at start of treatment and a median follow-up of 36 months (interquartile range, 18-60 months). At presentation, VA was better than or equal to 20/50 in 199 patients (64%) and better than or equal to 20/200 in 289 patients (93%). By Kaplan-Meier analysis, VA less than 20/200 at 3 years was not associated with sex, diabetes, systemic hypertension, or hypercholesterolemia but was associated with history of ocular comorbidities, type of isotope (ruthenium 106 or iodine 125), and initial VA ( >20/50 or <20/50). By multivariable analysis, age (hazard ratio [HR], 0.97; 95% CI, 0.94-1.00; P = .06), largest basal diameter (HR, 1.25; 95% CI, 1.16-1.34; P = <.001), total radiation dose to the fovea (HR, 1.03; 95% CI, 1.01-1.04; P = .001) and optic disc (HR, 1.01; 95% CI, 1.00-1.01; P = .005), and initial VA worse than 20/50 (HR, 1.85; 95% CI, 1.20-2.85; P = .005) were predictive of vision loss to a VA of less than 20/200. The concordance index for the full data set was 0.77. Using these data, an online risk calculator was developed to predict vision loss following episcleral brachytherapy. CONCLUSIONS AND RELEVANCE: The vision prognostication tool presented herein needs to be validated by independent data sets. This tool may improve counseling for patients being evaluated for episcleral brachytherapy. At-risk individuals identified by this tool could be considered for inclusion into trials exploring prevention or treatment of radiation retinopathy and alternative therapies of uveal melanoma.

Fine-needle aspiration biopsy of uveal melanoma: outcomes and complications.

PURPOSE: To report outcomes and complications of fine-needle aspiration biopsy (FNAB) of uveal melanoma performed for diagnostic and prognostic purposes. METHODS: Prospective interventional case series of 150 consecutive patients with a clinical diagnosis of uveal melanoma. The FNAB approach (transcorneal (TCO), transscleral (TSC) and transvitreal (TVT) was primarily determined by the location of the tumour. The FNAB was performed using a 25-gauge needle using a previously published technique. Prognostication was done using fluorescent in situ hybridisation detection of monosomy of chromosome 3. RESULTS: FNAB was obtained via TCO (8), TSC (71) and TVT (64) approach and impression smear in seven cases. Diagnostic yield was 92%. False-negative results were observed in 8%. Diagnostic yield was significantly correlated to biopsy approach (TCO 100%, TSC 96%, TSV 86%; p=0.029) and tumour size (basal diameter >5.0 mm; height >2.5 mm). Persistent haemorrhage (subretinal haemorrhage or vitreous) requiring surgical intervention (1%) and rhegmatogenous retinal detachment (1%) were rare. Endophthalmitis, hypotony, tumour recurrence, episcleral seeding were not observed over the average follow-up of 37 months. Prognostication could be performed in 85% of cases. Overall, only 47% of eligible patients enrolled into the adjuvant therapy trial. CONCLUSIONS: FNAB for uveal melanoma with 25-gauge needle is a safe procedure that can yield diagnostic and prognostic information in vast majority of cases (92% and 85%, respectively). Even so, only about half of the eligible cases eventually enrolled into the adjuvant therapy trial. Possibility of negative FNAB yield should be considered when counselling patients with small tumours. Alternative means of diagnostic biopsy and methods of prognostication need to be assessed for small tumours.

Inferring an Evolutionary Tree of Uveal Melanoma From Genomic Copy Number Aberrations.

PURPOSE: The purpose of this study is to study the genomic evolution of primary uveal melanoma. METHODS: Primary uveal melanoma genomic DNA was assayed on the Illumina Human660W-Quad v1.0 DNA Analysis BeadChip. Raw signal intensity data were quantile normalized to estimate copy number aberration with the Genome Alteration Print algorithm. Distance between samples was calculated as the Manhattan distance between the copy number profiles of the tumors. From the distance matrix, a phylogenetic network (evolutionary relationship inference) was estimated using SplitsTree4. RESULTS: Of the 57 tumors, one (1.8%) was discarded because of a failed assay, and seven (12.3%) were revealed to be mixtures of several cell populations that could not be resolved. Three clades of tumor were identified (A [59.2%], B [32.7%], and C [6.1%]), each following a distinct evolutionary path and each associated with metastatic status (P = 0.01). One tumor (2.0%) did not fit into any clade. From a normal diploid melanocyte, a few tumors (clade C) lose a large portion of chromosome 6q, but do not develop any mutations on 8q. In an alternate path, the vast majority of tumors (clade A and clade B [91.9%]) gain a copy of the telomeric half of 8q. A majority of these tumors (clade A) subsequently lose a copy of chromosome 3, as well as gain the centromeric half of 8q. The other tumors (clade B) gain copies of 6p, as well as regions on 11p and 22q. CONCLUSIONS: Our data suggest that there is little overlap in the subtypes of uveal melanoma after divergence (identified as clades A and B) and that these distinct subtypes are not likely to crossover or transform from one major clade to another.