Publications by authors named "Zelia M Correa"

64 Publications

Non-invasive evaluation of toxicity in vitreoretinal domain following insertion of sustained release methotrexate micro-implant.

Exp Eye Res 2021 Apr 19;205:108505. Epub 2021 Feb 19.

Department of Mechanical and Materials Engineering, University of Cincinnati, Cincinnati, OH, USA. Electronic address:

Purpose: To evaluate the safety and toxicity profile of a chitosan (CS) and poly(lactic-co-glycolic) acid (PLGA)-based sustained release methotrexate (MTX) intravitreal micro-implant in normal rabbit eyes using non-invasive testing that included electroretinography (ERG), ultrasound biomicroscopy (US), slit-lamp biomicroscopy (SLB), funduscopy, and intraocular pressure (IOP).

Methods: PLGA-coated CS-based micro-implants containing 400 μg of MTX and placebo (without drug) micro-implants were surgically-implanted in the vitreous of the right and the left eyes, respectively, in each of the thirty New Zealand rabbits. ERG, US, SLB, funduscopy, and IOP were assessed in both eyes at pre-determined time points (days: 1, 3, 7, 14, 28 and 56). The safety of micro-implants was assessed by analyzing the ERG data using different statistical models, to quantify and compare the functional integrity of the retina. Further, US, funduscopy, SLB and IOP determined the condition of the retina, the micro-implant and associated intraocular features.

Results: Statistical analyses of the ERG data showed unchanged functional integrity of retina between eyes with the PLGA-coated CS-based MTX micro-implant and the placebo micro-implant. US analysis showed that micro-implants were stationary throughout the study. SLB, funduscopy and IOP further confirmed that there were no abnormalities in the intraocular physiology.

Conclusion: The findings from ERG, US, SLB, funduscopy, and IOP showed no detectable adverse effects caused by our biodegradable micro-implants. These non-invasive techniques appeared to show lack of significant ocular toxicity over time in spite of degradation and changes in morphology of the micro-implants following intraocular implantation.
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http://dx.doi.org/10.1016/j.exer.2021.108505DOI Listing
April 2021

Impact of Genetic Ancestry on Prognostic Biomarkers in Uveal Melanoma.

Cancers (Basel) 2020 Oct 31;12(11). Epub 2020 Oct 31.

Bascom Palmer Eye Institute, Department of Ophthalmology, Miami, FL 33133, USA.

Uveal melanoma (UM) is the most common cancer of the eye and leads to metastatic death in up to half of patients. Genomic prognostic biomarkers play an important role in clinical management in UM. However, research has been conducted almost exclusively in patients of European descent, such that the association between genetic admixture and prognostic biomarkers is unknown. In this study, we compiled 1381 control genomes from West African, European, East Asian, and Native American individuals, assembled a bioinformatic pipeline for assessing global and local ancestry, and performed an initial pilot study of 141 UM patients from our international referral center that manages many admixed individuals. Global and local estimates were associated with genomic prognostic determinants. Expression quantitative trait loci (eQTL) analysis was performed on variants found in segments. Globally, after correction for multiple testing, no prognostic variable was significantly enriched in a given ancestral group. However, there was a trend suggesting an increased proportion of European ancestry associated with expression of the PRAME oncogene (q = 0.06). Locally enriched European haplotypes were associated with the poor prognosis class 2 gene expression profile and with genes involved in immune regulation (q = 4.7 × 10). These findings reveal potential influences of genetic ancestry on prognostic variables, implicate immune genes in prognostic differences based on ancestry, and provide a basis for future studies of admixed patients with UM using rigorous genetic ancestry methodology.
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http://dx.doi.org/10.3390/cancers12113208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693692PMC
October 2020

Isolated choroidal melanocytosis: clinical update on 37 cases.

Graefes Arch Clin Exp Ophthalmol 2020 Dec 9;258(12):2819-2829. Epub 2020 Sep 9.

Department of Ophthalmology, University of Cincinnati College of Medicine, Medical Science Building, Room 5306, Cincinnati, OH, 45267-0527, USA.

Purpose: Isolated choroidal melanocytosis is a congenital melanocytic hyperpigmentation involving the choroid that is not associated with iridic or scleral features of ocular melanocytosis. The purpose of this work was to describe the clinical features and course of a relatively large series of patients with this disorder.

Methods: A retrospective clinical study of 37 patients with isolated choroidal melanocytosis encountered in a single practice 1986-2018 was done. All lesions were 5 mm or larger in the largest basal diameter, homogeneously melanotic, and completely flat by conventional ocular ultrasonography.

Results: The 37 patients ranged in age from 2 weeks to 87 years (mean 31.5 years, median 18 years) at initial diagnosis of the melanotic choroidal lesion. Arc length largest basal diameter of the melanotic choroidal lesion ranged from 5.5 to 37 mm (mean 14.6 mm, median 13 mm). The lesion extended beneath the fovea in 18 eyes and to the optic disc margin in 6 eyes. Ten of the lesions straddled the ocular equator, but the center point of all of the lesions was posterior to the equator. The retina was fully attached and appeared normal over the melanotic choroidal lesion in each of these eyes. None of the melanotic choroidal lesions exhibited clumps of orange pigment or drusen on its surface. The lesion was unilateral and unifocal in 36 of the 37 patients. One patient had bilateral choroidal melanocytosis that was isolated in one eye but associated with partial iris melanocytosis in the fellow eye. Three adult patients had a choroidal melanoma localized to the patch of choroidal melanocytosis at baseline. One other adult patient had a choroidal melanoma in the fellow eye at baseline. One pediatric patient had viable unilateral non-familial retinoblastoma in the fellow eye and two adult patients had a classic choroidal nevus in the fellow eye. None of the flat patches of choroidal melanocytosis that were monitored periodically after initial diagnosis expanded appreciably during follow-up ranging from 4.9 months to 15.2 years (mean 5.0 years, median 2.3 years).

Conclusions: Isolated choroidal melanocytosis is a distinct clinical entity that must be distinguished from broad-based choroidal nevus, choroidal melanocytoma, small choroidal malignant melanoma, acquired bilateral patchy-streaky choroidal melanocytic fundopathy associated with disorders such as cutaneous vitiligo and Waardenburg syndrome, acquired bilateral zonal choroidal melanocytic fundopathy, and diffuse uveal melanocytic proliferation associated with systemic cancer. This disorder appears to predispose affected eyes to development of choroidal melanoma arising from the hypermelanotic patch.
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http://dx.doi.org/10.1007/s00417-020-04919-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677270PMC
December 2020

Successful growth of fresh retinoblastoma cells in chorioallantoic membrane.

Int J Retina Vitreous 2020 29;6:33. Epub 2020 Jul 29.

Department of Ophthalmology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.

The authors developed a retinoblastoma model using fresh harvested cells from an enucleated eye that were transplanted in chick embryos (chorioallantoic membrane model). The transplanted embryos were treated with escalating doses of Melphalan. This exploratory model was developed with the goal of testing drug sensitivity. Our findings suggest this tumor model could be employed to personalize treatment for patients with retinoblastoma, especially those with bilateral and more refractory disease.
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http://dx.doi.org/10.1186/s40942-020-00236-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391810PMC
July 2020

Gene Expression Profile Prediction in Uveal Melanoma Using Deep Learning: A Pilot Study for the Development of an Alternative Survival Prediction Tool.

Ophthalmol Retina 2020 12 18;4(12):1213-1215. Epub 2020 Jun 18.

Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland; Department of Ophthalmology, University of Cincinnati College of Medicine, Cincinnati, Ohio.

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http://dx.doi.org/10.1016/j.oret.2020.06.023DOI Listing
December 2020

Global Retinoblastoma Presentation and Analysis by National Income Level.

Authors:
Ido Didi Fabian Elhassan Abdallah Shehu U Abdullahi Rula A Abdulqader Sahadatou Adamou Boubacar Dupe S Ademola-Popoola Adedayo Adio Armin R Afshar Priyanka Aggarwal Ada E Aghaji Alia Ahmad Marliyanti N R Akib Lamis Al Harby Mouroge H Al Ani Aygun Alakbarova Silvia Alarcón Portabella Safaa A F Al-Badri Ana Patricia A Alcasabas Saad A Al-Dahmash Amanda Alejos Ernesto Alemany-Rubio Amadou I Alfa Bio Yvania Alfonso Carreras Christiane Al-Haddad Hamoud H Y Al-Hussaini Amany M Ali Donjeta B Alia Mazin F Al-Jadiry Usama Al-Jumaily Hind M Alkatan Charlotta All-Eriksson Ali A R M Al-Mafrachi Argentino A Almeida Khalifa M Alsawidi Athar A S M Al-Shaheen Entissar H Al-Shammary Primawita O Amiruddin Romanzo Antonino Nicholas J Astbury Hatice T Atalay La-Ongsri Atchaneeyasakul Rose Atsiaya Taweevat Attaseth Than H Aung Silvia Ayala Baglan Baizakova Julia Balaguer Ruhengiz Balayeva Walentyna Balwierz Honorio Barranco Covadonga Bascaran Maja Beck Popovic Raquel Benavides Sarra Benmiloud Nissrine Bennani Guebessi Rokia C Berete Jesse L Berry Anirban Bhaduri Sunil Bhat Shelley J Biddulph Eva M Biewald Nadia Bobrova Marianna Boehme H C Boldt Maria Teresa B C Bonanomi Norbert Bornfeld Gabrielle C Bouda Hédi Bouguila Amaria Boumedane Rachel C Brennan Bénédicte G Brichard Jassada Buaboonnam Patricia Calderón-Sotelo Doris A Calle Jara Jayne E Camuglia Miriam R Cano Michael Capra Nathalie Cassoux Guilherme Castela Luis Castillo Jaume Català-Mora Guillermo L Chantada Shabana Chaudhry Sonal S Chaugule Argudit Chauhan Bhavna Chawla Violeta S Chernodrinska Faraja S Chiwanga Tsengelmaa Chuluunbat Krzysztof Cieslik Ruellyn L Cockcroft Codruta Comsa Zelia M Correa Maria G Correa Llano Timothy W Corson Kristin E Cowan-Lyn Monika Csóka Xuehao Cui Isac V Da Gama Wantanee Dangboon Anirban Das Sima Das Jacquelyn M Davanzo Alan Davidson Patrick De Potter Karina Q Delgado Hakan Demirci Laurence Desjardins Rosdali Y Diaz Coronado Helen Dimaras Andrew J Dodgshun Craig Donaldson Carla R Donato Macedo Monica D Dragomir Yi Du Magritha Du Bruyn Kemala S Edison I Wayan Eka Sutyawan Asmaa El Kettani Amal M Elbahi James E Elder Dina Elgalaly Alaa M Elhaddad Moawia M Ali Elhassan Mahmoud M Elzembely Vera A Essuman Ted Grimbert A Evina Zehra Fadoo Adriana C Fandiño Mohammad Faranoush Oluyemi Fasina Delia D P G Fernández Ana Fernández-Teijeiro Allen Foster Shahar Frenkel Ligia D Fu Soad L Fuentes-Alabi Brenda L Gallie Moira Gandiwa Juan L Garcia David García Aldana Pascale Y Gassant Jennifer A Geel Fariba Ghassemi Ana V Girón Zelalem Gizachew Marco A Goenz Aaron S Gold Maya Goldberg-Lavid Glen A Gole Nir Gomel Efren Gonzalez Graciela Gonzalez Perez Liudmira González-Rodríguez Henry N Garcia Pacheco Jaime Graells Liz Green Pernille A Gregersen Nathalia D A K Grigorovski Koffi M Guedenon D Sanjeeva Gunasekera Ahmet K Gündüz Himika Gupta Sanjiv Gupta Theodora Hadjistilianou Patrick Hamel Syed A Hamid Norhafizah Hamzah Eric D Hansen J William Harbour M Elizabeth Hartnett Murat Hasanreisoglu Sadiq Hassan Shadab Hassan Stanislava Hederova Jose Hernandez Lorelay Marie Carcamo Hernandez Laila Hessissen Diriba F Hordofa Laura C Huang G B Hubbard Marlies Hummlen Kristina Husakova Allawi N Hussein Al-Janabi Russo Ida Vesna R Ilic Vivekaraj Jairaj Irfan Jeeva Helen Jenkinson Xunda Ji Dong Hyun Jo Kenneth P Johnson William J Johnson Michael M Jones Theophile B Amani Kabesha Rolande L Kabore Swathi Kaliki Abubakar Kalinaki Mehmet Kantar Ling-Yuh Kao Tamar Kardava Rejin Kebudi Tomas Kepak Naama Keren-Froim Zohora J Khan Hussain A Khaqan Phara Khauv Wajiha J Kheir Vikas Khetan Alireza Khodabande Zaza Khotenashvili Jonathan W Kim Jeong Hun Kim Hayyam Kiratli Tero T Kivelä Artur Klett Jess Elio Kosh Komba Palet Dalia Krivaitiene Mariana Kruger Kittisak Kulvichit Mayasari W Kuntorini Alice Kyara Eva S Lachmann Carol P S Lam Geoffrey C Lam Scott A Larson Slobodanka Latinovic Kelly D Laurenti Bao Han A Le Karin Lecuona Amy A Leverant Cairui Li Ben Limbu Quah Boon Long Juan P López Robert M Lukamba Livia Lumbroso Sandra Luna-Fineman Delfitri Lutfi Lesia Lysytsia George N Magrath Amita Mahajan Abdul Rahim Majeed Erika Maka Mayuri Makan Emil K Makimbetov Chatonda Manda Nieves Martín Begue Lauren Mason John O Mason Ibrahim O Matende Miguel Materin Clarissa C D S Mattosinho Marchelo Matua Ismail Mayet Freddy B Mbumba John D McKenzie Aurora Medina-Sanson Azim Mehrvar Aemero A Mengesha Vikas Menon Gary John V D Mercado Marilyn B Mets Edoardo Midena Divyansh K C Mishra Furahini G Mndeme Ahmed A Mohamedani Mona T Mohammad Annette C Moll Margarita M Montero Rosa A Morales Claude Moreira Prithvi Mruthyunjaya Mchikirwa S Msina Gerald Msukwa Sangeeta S Mudaliar Kangwa I Muma Francis L Munier Gabriela Murgoi Timothy G Murray Kareem O Musa Asma Mushtaq Hamzah Mustak Okwen M Muyen Gita Naidu Akshay Gopinathan Nair Larisa Naumenko Paule Aïda Ndoye Roth Yetty M Nency Vladimir Neroev Hang Ngo Rosa M Nieves Marina Nikitovic Elizabeth D Nkanga Henry Nkumbe Murtuza Nuruddin Mutale Nyaywa Ghislaine Obono-Obiang Ngozi C Oguego Andrzej Olechowski Scott C N Oliver Peter Osei-Bonsu Diego Ossandon Manuel A Paez-Escamilla Halimah Pagarra Sally L Painter Vivian Paintsil Luisa Paiva Bikramjit P Pal Mahesh Shanmugam Palanivelu Ruzanna Papyan Raffaele Parrozzani Manoj Parulekar Claudia R Pascual Morales Katherine E Paton Katarzyna Pawinska-Wasikowska Jacob Pe'er Armando Peña Sanja Peric Chau T M Pham Remezo Philbert David A Plager Pavel Pochop Rodrigo A Polania Vladimir G Polyakov Manca T Pompe Jonathan J Pons Daphna Prat Vireak Prom Ignatius Purwanto Ali O Qadir Seema Qayyum Jiang Qian Ardizal Rahman Salman Rahman Jamalia Rahmat Purnima Rajkarnikar Rajesh Ramanjulu Aparna Ramasubramanian Marco A Ramirez-Ortiz Léa Raobela Riffat Rashid M Ashwin Reddy Ehud Reich Lorna A Renner David Reynders Dahiru Ribadu Mussagy M Riheia Petra Ritter-Sovinz Duangnate Rojanaporn Livia Romero Soma R Roy Raya H Saab Svetlana Saakyan Ahmed H Sabhan Mandeep S Sagoo Azza M A Said Rohit Saiju Beatriz Salas Sonsoles San Román Pacheco Gissela L Sánchez Phayvanh Sayalith Trish A Scanlan Amy C Schefler Judy Schoeman Ahad Sedaghat Stefan Seregard Rachna Seth Ankoor S Shah Shawkat A Shakoor Manoj K Sharma Sadik T Sherief Nandan G Shetye Carol L Shields Sorath Noorani Siddiqui Sidi Sidi Cheikh Sónia Silva Arun D Singh Niharika Singh Usha Singh Penny Singha Rita S Sitorus Alison H Skalet Hendrian D Soebagjo Tetyana Sorochynska Grace Ssali Andrew W Stacey Sandra E Staffieri Erin D Stahl Christina Stathopoulos Branka Stirn Kranjc David K Stones Caron Strahlendorf Maria Estela Coleoni Suarez Sadia Sultana Xiantao Sun Meryl Sundy Rosanne Superstein Eddy Supriyadi Supawan Surukrattanaskul Shigenobu Suzuki Karel Svojgr Fatoumata Sylla Gevorg Tamamyan Deborah Tan Alketa Tandili Fanny F Tarrillo Leiva Maryam Tashvighi Bekim Tateshi Edi S Tehuteru Luiz F Teixeira Kok Hoi Teh Tuyisabe Theophile Helen Toledano Doan L Trang Fousseyni Traoré Sumalin Trichaiyaporn Samuray Tuncer Harba Tyau-Tyau Ali B Umar Emel Unal Ogul E Uner Steen F Urbak Tatiana L Ushakova Rustam H Usmanov Sandra Valeina Milo van Hoefen Wijsard Adisai Varadisai Liliana Vasquez Leon O Vaughan Nevyana V Veleva-Krasteva Nishant Verma Andi A Victor Maris Viksnins Edwin G Villacís Chafla Vicktoria Vishnevskia-Dai Tushar Vora Antonio E Wachtel Werner Wackernagel Keith Waddell Patricia D Wade Amina H Wali Yi-Zhuo Wang Avery Weiss Matthew W Wilson Amelia D C Wime Atchareeya Wiwatwongwana Damrong Wiwatwongwana Charlotte Wolley Dod Phanthipha Wongwai Daoman Xiang Yishuang Xiao Jason C Yam Huasheng Yang Jenny M Yanga Muhammad A Yaqub Vera A Yarovaya Andrey A Yarovoy Huijing Ye Yacoub A Yousef Putu Yuliawati Arturo M Zapata López Ekhtelbenina Zein Chengyue Zhang Yi Zhang Junyang Zhao Xiaoyu Zheng Katsiaryna Zhilyaeva Nida Zia Othman A O Ziko Marcia Zondervan Richard Bowman

JAMA Oncol 2020 05;6(5):685-695

International Centre for Eye Health, London School of Hygiene & Tropical Medicine, London, United Kingdom.

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.
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http://dx.doi.org/10.1001/jamaoncol.2019.6716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7047856PMC
May 2020

Clinical implications of biopsy for posterior uveal melanoma.

Arq Bras Oftalmol 2019 24;82(6):1-2. Epub 2019 Oct 24.

Department of Ophthalmology, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.

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http://dx.doi.org/10.5935/0004-2749.20190104DOI Listing
March 2020

ALTERNATIVE MANAGEMENT OF CIRCUMSCRIBED CHOROIDAL HEMANGIOMA USING INTRAVITREAL METOPROLOL.

Retin Cases Brief Rep 2019 Sep 10. Epub 2019 Sep 10.

Departments of Ophthalmology and Oncology, Wilmer Eye Institute, Sidney Kimmel Comprehensive Cancer Institute, John Hopkins Medicine, Baltimore, Maryland.

Background/purpose: To describe a patient with visually symptomatic circumscribed choroidal hemangioma (CCH) treated successfully with intravitreal beta-blocker.

Methods: This is an interventional single case report of a 63 year-old man with a juxtafoveal CCH and extensive subretinal fluid (SRF) unsuccessfully treated with intravitreal anti-VEGF. Off-label intravitreal use of metoprolol (50μg/0.05 ml) was then performed. Main outcome measures were resolution or decreased subretinal fluid on OCT, visual stability or improvement, lack of retinal/ocular toxicity.

Results: Following 2 intravitreal injections of metoprolol (1 month apart), significant response was observed with decrease of SRF and visual improvement to 20/400 during a 9-week follow-up after the injections.

Conclusion: These preliminary findings suggest that intravitreal metoprolol can be a safe alternative treatment for patients with CCH. This off-label therapy could represent another option for patients with this condition.
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http://dx.doi.org/10.1097/ICB.0000000000000917DOI Listing
September 2019

Survival of Young Patients With Posterior Uveal Melanoma-Reply.

JAMA Ophthalmol 2019 Jul 18. Epub 2019 Jul 18.

Department of Ophthalmology, College of Medicine, University of Cincinnati, Cincinnati, Ohio.

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http://dx.doi.org/10.1001/jamaophthalmol.2019.2552DOI Listing
July 2019

Relationship between clinical features, GEP class, and PRAME expression in uveal melanoma.

Graefes Arch Clin Exp Ophthalmol 2019 Jul 7;257(7):1541-1545. Epub 2019 May 7.

University of Cincinnati, Cincinnati, OH, USA.

Background: Metastatic risk for uveal melanoma (UM) patients can be characterized by gene expression profiling (GEP) (Castle Biosciences, Friendswood, TX). Class 1A tumors carry low metastatic risk; class 1B tumors have intermediate risk; and class 2 tumors have high risk. Preferentially expressed antigen in melanoma (PRAME) is a tumor-associated antigen which is expressed in various neoplasms including UM. Recently, PRAME expression in uveal melanoma was first recognized to confer an additional metastatic risk beyond GEP status.

Methods: This was a retrospective, consecutive, multicenter chart review study. All patients diagnosed with UM at two major ocular oncology centers from August 2016 to February 2018 who underwent both GEP and PRAME mRNA expression testing were included. Patient age at diagnosis, gender, and tumor variables such as thickness, largest basal diameter (LBD), tumor volume, TNM stage, and GEP class and PRAME status were extracted from the medical records. Statistical analysis was performed to analyze the association of PRAME +/- status with all clinical and molecular variables.

Results: One hundred forty-eight UM patients were identified. TNM was stage I in 51 (34.5%), stage IIA in 33 (22.3%), stage IIB in 34 (23%), stage IIIA in 20 (13.5%), and stage IIIB in 10 (6.8%) patients. Fifty-five patients (37%) were PRAME-positive, a significant fraction. There was no association between higher TNM stage and positive PRAME status (p = 0.129). PRAME expression was found to be independent of gender, patient age, and tumor thickness. PRAME expression was statistically associated with LBD and tumor volume. Higher GEP class was associated with higher TNM staging (p < 0.001). Worsening GEP class was associated with PRAME+ status with 28% of GEP class 1A tumors having PRAME+ status, 29% of GEP class 1B tumors having PRAME+ status, and 56% of GEP class 2 tumors having PRAME+ status.

Conclusions: In this study cohort, PRAME+ status was significantly associated with LBD and tumor volume as well as worsening GEP class. Nearly a third of GEP class 1A tumors expressed PRAME. Given the recent published data on increased metastatic risk among patients with tumors expressing PRAME, this study suggests that a significant fraction of 1A patients may harbor an increased metastatic risk. Future large, multicenter studies with long-term follow-up will clarify this finding.
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http://dx.doi.org/10.1007/s00417-019-04335-wDOI Listing
July 2019

Trends in Radiation Practices for Female Ocular Oncologists in North America: A Collaborative Study of the International Society of Ocular Oncology.

Ocul Oncol Pathol 2019 Jan 12;5(1):54-59. Epub 2018 Jun 12.

USC Roski Eye Institute, University of Southern California, Los Angeles, California, USA.

Background: The aim of this study was to determine the known radiation exposure, attitudes, and consequent risk modifications among female ocular oncologists in North America who routinely administer radioactive plaque brachytherapy treatment and are members of the International Society of Ocular Oncology.

Methods: Nineteen female ocular oncologists completed an anonymous 17-question radiation exposure survey.

Results: Eleven of the participants chose to routinely wear lead protection during surgery; 8 did not. Fifteen of 19 participants reported using an unloaded "nonactive" template to prepare for plaque implantation. During pregnancy, 11 of 13 participants continued to perform plaque brachytherapy. Eight of these 11 undertook measures to decrease radiation exposure self-reported as lead wear and other. The average reported anxiety regarding fertility was 2.1 (SD, 2.2) on a scale from 1 to 10.

Conclusion: This study corroborates prior literature that surgeons' exposure to radiation during plaque brachytherapy is minimal. Nonetheless, there remains some anxiety regarding exposure risk to women, due to potential effects on fertility and fetal health. We found variability in exposure monitoring, required training, and precautions during pregnancy amongst this group of surgeons. Improved education and clearer pregnancy guidelines may equip female ocular oncologists with optimal knowledge regarding risk of radiation exposure.
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http://dx.doi.org/10.1159/000489219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341326PMC
January 2019

Eye-Sparing Treatment for Diffuse Invasive Conjunctival Melanoma.

Ocul Oncol Pathol 2018 Jun 1;4(4):261-266. Epub 2018 Feb 1.

Department of Ophthalmology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.

The management of patients with diffuse invasive conjunctival melanoma focuses on local tumor control and screening for metastasis. Despite the lack of consensus on the benefit of sentinel lymph node biopsy for these neoplasms, the information obtained by histopathology is useful for tumor staging and treatment planning. Due to the lack of evidence of survival improvement, orbital exenteration is being performed with diminishing frequency. We describe a patient with diffuse invasive conjunctival melanoma and lymph node involvement treated by tumor debulking, brachytherapy (custom unshielded radioactive device), and adjuvant ipilimumab who has had a favorable outcome without emergence of local tumor relapse or distant metastasis during 16 months of follow up.
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http://dx.doi.org/10.1159/000485978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6322084PMC
June 2018

Late Apical Recurrence of Choroidal Melanoma 10 Years after Successful Treatment with Brachytherapy.

Ocul Oncol Pathol 2018 Jun 22;4(4):225-229. Epub 2017 Dec 22.

University of Southern California Roski Eye Institute, Los Angeles, CA, USA.

Purpose: To describe late apical relapse of a choroidal melanoma at the site of fine needle aspiration biopsy 10 years following successful treatment with I brachytherapy.

Methods: Retrospective case report of a 78-year-old male presenting 10 years following successful I brachytherapy for a choroidal melanoma with a medium-sized nodular amelanotic tumor recurrence at the site of the prior tumor biopsy.

Results: Fundus photography and B-scan ultrasound documented the findings at presentation at our institution. The patient was followed closely for 8 weeks while information was retrieved from the treating institution. During this short period, there was significant apical tumor growth. Additionally, there was a clear clinical change compared to the last documented photos from 5 years prior at the treating institution. Enucleation was recommended. Pathological analysis confirmed the diagnosis of recurrent choroidal melanoma at the apex of the treated lesion, at the site of prior biopsy. Systemic surveillance was negative for metastatic disease.

Conclusion: Current literature suggests the majority of choroidal melanoma recurrences occur within 5 years following treatment. However, this case of recurrence 10 years after brachytherapy emphasizes the importance of life-long ophthalmic care for these patients. Additionally, this case demonstrates the possibility of a rare recurrence at a prior biopsy site.
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http://dx.doi.org/10.1159/000485131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6322081PMC
June 2018

Posterior uveal melanoma in adolescents and children: current perspectives.

Clin Ophthalmol 2018 7;12:2205-2212. Epub 2018 Nov 7.

Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA,

Recognizing that <1% of all uveal melanomas occur in young persons, and that very few clinicians encounter more than a few such cases over an extended career, we felt that a retrospective review of literature and sharing of our clinical experience would be appropriate to remind readers about this age subgroup of patients with posterior uveal melanoma. This interest stems from the increase in reported cases of uveal melanoma in younger individuals and recent advances in the field.
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http://dx.doi.org/10.2147/OPTH.S142984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6228084PMC
November 2018

Clinical Features, Metastasis, and Survival in Patients Younger Than 21 Years With Posterior Uveal Melanoma.

JAMA Ophthalmol 2019 01;137(1):75-81

Department of Ophthalmology, College of Medicine, University of Cincinnati, Cincinnati, Ohio.

Importance: Given the rarity of posterior uveal melanoma in patients younger than 21 years, reporting clinical experience in this area has relevance.

Objective: To describe the baseline clinical features, treatment, and clinical course of a group of patients younger than 21 years who have primary posterior uveal melanoma.

Design, Setting, And Participants: This retrospective descriptive case series of patients younger than 21 years who have a primary choroidal or ciliochoroidal melanoma was conducted at a single-center subspecialty referral practice. Patients in the relevant age group who were treated in a single practice between July 1980 and December 2013 were included; clinical data collected through December 2017 were captured to permit adequate follow-up time in all cases.

Main Outcomes And Measures: Conventional descriptive statistics of relevant clinical variables (eg, demographic, tumor, treatment, and outcome variables) of each patient were recorded. Actuarial metastasis-free and overall survival curves were computed and plotted, as was a postdetection survival curve of patients who developed metastasis during available follow-up.

Results: Of 2265 patients with posterior uveal melanoma encountered by the authors during the study interval, 18 (0.8%) were younger than 21 years when diagnosed and treated. Ten were female and 8 male, and the mean (SD) age was 16.6 (4.2) years. Through available follow-up, 8 of these patients had developed metastatic uveal melanoma (44%). All 8 died of metastasis. Actuarial survival analysis showed that the cumulative probability of metastatic death in this group exceeded 50%. The median overall survival time after treatment of the primary intraocular tumor was 11.9 (95% CI, 7.3-16.5) years. The median survival time after detection of metastasis in the 8 patients who developed metastasis was 2.3 months (95% CI, 0.0-5.2) months.

Conclusions And Relevance: Posterior uveal melanoma in patients younger than 21 years appears to have a similar if not worse prognosis than patients with PUM in the population overall. Owing to the later onset of metastasis observed, patients younger than 21 years should continue to have surveillance tests for more than 10 years after treatment.
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http://dx.doi.org/10.1001/jamaophthalmol.2018.5132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6439783PMC
January 2019

Unilateral retinoblastoma with contralateral isolated choroidal Melanocytosis: case report of an unexpected presentation.

BMC Ophthalmol 2018 Sep 17;18(1):251. Epub 2018 Sep 17.

Department of Ophthalmology, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

Background: Congenital ocular melanocytosis has been shown to be extremely uncommon in studies of numerous infants and children with retinoblastoma and disorders such as retinopathy of prematurity.

Case Presentation: A 33-month-old Caucasian boy presented with a solid white predominantly endophytic retinoblastoma filling most of the nasal aspect of the fundus and extensive vitreous seeding. Fundus exam of the contralateral eye showed a broad-based flat melanotic area of the choroid extending from the subfoveal region to the ora serrata temporally. The child was treated by enucleation of the retinoblastoma-containing eye (homozygous non-germline RB1 mutation) and is being monitored annually. The patient has been followed for 4 years.

Conclusions: This rare presentation of advanced unilateral retinoblastoma and contralateral isolated choroidal melanocytosis in a young child emphasizes the importance of detailed fundus mapping of the non-affected eye and has potential implications due to the increased incidence of uveal melanoma later in life.
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http://dx.doi.org/10.1186/s12886-018-0916-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6142679PMC
September 2018

Are Risk Factors for Growth of Choroidal Nevi Associated With Malignant Transformation? Assessment With a Validated Genomic Biomarker.

Am J Ophthalmol 2019 01 7;197:168-179. Epub 2018 Sep 7.

Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland, USA.

Purpose: To test the hypothesis that widely used clinical risk factors for growth of choroidal nevi are associated with malignant transformation.

Methods: Fine needle biopsy for assignment of gene expression profile (class 1 or class 2) was performed in 207 choroidal melanocytic tumors < 3.5 mm in thickness. The class 2 profile was employed as a validated biomarker for malignant transformation. The following data were collected: patient age and sex, tumor diameter and thickness, distance of posterior tumor margin from the optic disc, and the presence or absence of serous retinal detachment, orange lipofuscin pigment, drusen, retinal pigment epithelial fibrosis, retinal pigment epithelial atrophy, visual symptoms, and documented tumor growth.

Results: Clinical features associated with the class 2 profile included patient age > 60 years and tumor thickness > 2.25 mm (Fisher exact test, P = .002 for both). Documented growth was not associated with the class 2 profile (P = .5). The odds ratio of a tumor having the class 2 profile was 2.8 (95% confidence interval 1.3-5.9) for patient age > 60 years and 3.5 (95% confidence interval 1.4-8.8) for tumor thickness > 2.25 mm. For patients with both risk factors, the "number needed to treat" to identify 1 patient with a class 2 tumor was 4.3 (P = .0002). No other clinical feature or combination of features was associated with the class 2 profile.

Conclusions: None of the widely used choroidal nevus risk factors for tumor growth, nor documented growth itself, is pathognomonic of malignant transformation as defined by class 2 gene expression profile. Patient age and tumor thickness may be helpful for identifying small choroidal melanocytic tumors that are more likely to have the class 2 profile. Observation for growth prior to treatment continues to be reasonable for most patients with suspicious choroidal nevi. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.
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http://dx.doi.org/10.1016/j.ajo.2018.08.045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6291343PMC
January 2019

Scleral necrosis in patients with posterior uveal melanomas evaluated by transcleral fine needle aspiration biopsy and treated by 125I plaque.

Arq Bras Oftalmol 2018 Jul-Aug;81(4):330-335

Department of Ophthalmology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.

Purpose: To evaluate the incidence, potential correlation with transcleral fine needle aspiration biopsy, and treatment of scleral necrosis in patients with posterior uveal melanomas treated by 125I plaque radiotherapy and assessed by transcleral fine needle aspiration biopsy.

Methods: We per-formed a retrospective review of posterior uveal melanoma treated by 125I plaque radiotherapy at a single academic institution between July 2006 and July 2013. Consecutive patients diagnosed with a posterior uveal melanoma during the study period that had an anterior margin at or anterior to the equator who were evaluated by transcleral fine needle aspiration biopsy prior to 125I plaque radiotherapy were included. The main outcome measure was development of scleral necrosis, and the secondary outcome was treatment of this complication. Statistical analysis included computation of conventional descriptive statistics, cross-tabulation and chi-square tests of potential factors related to the development of scleral necrosis, and summarizing of treatment approaches and results. The incidence of treatment of scleral necrosis was calculated using the Kaplan-Meier method.

Results: During the 7-year study period, 87 posterior uveal melanomas were evaluated by transcleral fine needle aspiration biopsy and treated by 125I plaque radiotherapy. The median largest basal diameter of the tumor was 13.3 mm, and the median thickness was 6.8 mm. Eight patients (9.2%) developed scleral necrosis during follow-up. Thicker tumors (> 6.5 mm) were more likely to develop scleral necrosis (n=7) than thinner tumors (p=0.05). The median interval between 125I plaque radiotherapy and detection of scleral necrosis was 19.1 months. The overall cumulative probability of scleral necrosis was 6.2% at 6 months and 14.3% at 24 months, subsequently remaining stable. For thicker tumors, the probability of scleral necrosis was 23.5% at 45.4 months. Five patients were treated by scleral patch graft (62.5%) and three by observation (37.5%). One patient underwent enucleation after two failed scleral patch attempts and recurrent scleral necrosis. The mean follow-up period for patients with scleral necrosis was 34.5 months.

Conclusions: Thicker posterior uveal melanomas are more likely to develop scleral necrosis after 125I plaque radiotherapy and transcleral fine needle aspiration biopsy. While observation is sufficient for managing limited scleral necrosis, scleral patch graft is a viable alternative for eye preservation in extensive scleral necrosis.
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http://dx.doi.org/10.5935/0004-2749.20180064DOI Listing
October 2018

Mutation in Metastatic Uveal Melanoma and Treatment Outcome.

Case Rep Oncol Med 2018 4;2018:4256365. Epub 2018 Apr 4.

Department of Ophthalmology, University of Cincinnati, Cincinnati, OH, USA.

Metastatic prognosis in uveal melanoma is assessed by gene expression profiling (GEP) testing of the tumor cells, usually obtained by fine needle aspiration (FNA). GEP has demonstrated high accuracy in distinguishing class I and II tumors, both having different metastatic potential. Transcriptomic studies identified distinct mutations including somatic mutations in and , detected in more than 80%, and contribute to the upregulation of the mitogen-activated protein kinase (MAPK) pathway and the development of uveal melanoma (UM). The role of these mutations in treatment selection and possible benefit from targeted therapy are somewhat unclear. However, until the discovery of novel agents, local versus systemic therapies remain options for treatment that can still be considered for disease control in certain cases. We report a series of patients with metastatic UM with distinct mutational profiles. One had significant liver metastases with proven mutation on tissue biopsy while peripheral blood molecular profiling did not show these mutations. The other three cases had no mutation. All cases received nab-paclitaxel (Abraxane) as a treatment drug, and we record their responses to treatment and their molecular-profiling results.
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http://dx.doi.org/10.1155/2018/4256365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5904798PMC
April 2018

Reappraising the Psychosocial Needs of Patients With Uveal Melanoma.

Authors:
Zelia M Correa

JAMA Ophthalmol 2018 04;136(4):363-364

Department of Ophthalmology, Ocular Oncology and Ultrasonography Services, University of Cincinnati College of Medicine, Cincinnati, Ohio.

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http://dx.doi.org/10.1001/jamaophthalmol.2017.6576DOI Listing
April 2018

Comparison of Alternative Tumor Size Classifications for Posterior Uveal Melanomas.

Invest Ophthalmol Vis Sci 2017 07;58(9):3335-3342

Department of Ophthalmology, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States.

Purpose: Determine which posterior uveal melanoma (PUM) size classification with three categories has the best prognostic discrimination.

Methods: Single-institution study of 424 consecutive patients with PUM. The tumor's largest basal diameter (LBD), smallest basal diameter (SBD), and thickness (TH) were estimated by fundus mapping and ultrasonography. Tumors were assigned to "small," "medium," or "large" size categories defined by 11 different classifications (Linear LBD, Rectangular LBD × TH, Cubic LBD × SBD × TH, Warren Original, Warren Modified, Augsburger, COMS Original, COMS Revised, TNM 2002, and modified TNM 2010 classification [a,b]). Prognostic significance of classifications was evaluated by Kaplan-Meier event curves with computation of log rank test for trend statistic.

Results: In six classification systems (Warren Original, Warren Modified, COMS Revised, TNM 2002, TNM 2010a, TNM 2010b) >50% of tumors fell within one subgroup. In the Warren Original classification <5% of tumors fell within one subgroup. Separation of Kaplan-Meier curves among three size categories was judged "excellent" in four classifications (Linear LBD, Cubic Volume, TNM 2010a, and TNM 2010b) and "very poor" in the Warren Original. Linear LBD classification was associated with highest log rank statistic value. TNM 2010a, TNM 2010b, TNM 2002, Augsburger, and Cubic Volume classifications were also determined to be quite good.

Conclusions: Linear LBD classification was the best three-size category discriminator among low-, intermediate-, and high-risk subgroups. Considering our findings, it seems possible that the arduous work required to apply complex classifications, especially for three-category systems, for PUM may not be justified in routine clinical practice.
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http://dx.doi.org/10.1167/iovs.16-20465DOI Listing
July 2017

Clinical application of genetic testing for posterior uveal melanoma.

Int J Retina Vitreous 2016 1;2. Epub 2016 Feb 1.

University of Cincinnati College of Medicine, Medical Arts Building, 222 Piedmont Avenue, Suite 1500, Cincinnati, OH 45209 USA.

Uveal melanoma is the most common primary intraocular tumor in adults, and it has a strong potential to metastasize. Traditionally, clinicopathological features of these tumors were used to provide a limited prediction of the metastatic risk. However, early genetic studies using karyotype analysis, fluorescence in situ hybridization, and comparative genetic hybridization of posterior uveal melanoma samples identified multiple chromosomal abnormalities associated with a higher risk of fatal metastasis. This correlation between specific genetic abnormalities in uveal melanoma and a patient's risk for development of metastasis has recently been widely studied, and the development of new prognostic tests has allowed clinicians to predict this metastatic risk with increased accuracy. Such novel tests include gene expression profiling, which analyzes the RNA expression patterns of tumor cells, and multiplex ligation-dependent probe amplification, which detects deletions or and amplifications of DNA in tumor cells. This review discusses the current status of prognostic testing techniques available to clinicians and patients for posterior uveal melanomas.
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http://dx.doi.org/10.1186/s40942-016-0030-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5088449PMC
February 2016

Noninvasive Electroretinography Assessment of Intravitreal Sustained-Release Methotrexate Microimplants in Rabbit Eyes.

J Ocul Pharmacol Ther 2016 11 18;32(9):583-594. Epub 2016 Oct 18.

1 Department of Mechanical and Materials Engineering, University of Cincinnati , Cincinnati, Ohio.

Purpose: The purpose of this study is to noninvasively evaluate the safety and toxicity of a chitosan (CS) and polylactic acid (PLA)-based sustained-release methotrexate (MTX) intravitreal microimplant in normal rabbit eyes using electroretinography (ERG).

Methods: PLA-coated CS-based microimplants containing 400 μg of MTX and placebo microimplants (without drug) were surgically implanted in the vitreous of the right and the left eyes, respectively, in each of the 8 New Zealand rabbits using minimally invasive technique. At each predetermined time points (days 5, 12, 19, and 33), ERG was conducted on 2 rabbits to evaluate the safety of the microimplants administered in each eye. ERG was carried out using 2 protocols, scotopic and photopic, on each eye prior to surgery (PS) and prior to euthanasia (PE) conditions. The safety of the microimplants was assessed using statistical analysis of the ERG data (B/A ratio analysis, oscillatory potential analysis, and Naka-Rushton analysis) and subsequently quantifying and comparing functional integrity of the retina between the PS and PE conditions of each eye.

Results: Statistical analysis of the ERG data showed no change in retinal functional integrity because of the PLA-coated CS-based MTX microimplant and the placebo microimplant. ERG analysis also revealed absence of any evident bioelectrical dysfunction caused by the microimplants.

Conclusion: ERGs were performed to determine whether the microimplants containing MTX and the placebo microimplants were associated with any profound retinal bioelectrical dysfunction that might be attributable to toxicity not apparent on histological studies of such eyes. The results shown in this report indicate that there were no such evident adverse effects of the microimplants or contained drug.
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http://dx.doi.org/10.1089/jop.2016.0006DOI Listing
November 2016

Photoreceptor Arrangement Changes Secondary to Choroidal Nevus.

JAMA Ophthalmol 2016 Nov;134(11):1315-1319

Department of Ophthalmology, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, Brazil.

Importance: Although mostly asymptomatic, patients with choroidal nevi carry a moderate risk for malignant transformation and visual loss. A novel noninvasive imaging assessment could change the current clinical evaluation of choroidal nevi.

Observation: Three patients with a recent diagnosis of choroidal nevi underwent a novel adaptive optical assessment that detected potential photoreceptor abnormalities in the retina overlying the choroidal nevi.

Conclusions And Relevance: Adaptive optics imaging may provide high-resolution en face images of retinal structural changes in the photoreceptor mosaic overlying the choroidal nevi. Cone attenuation may be an important component of structural damage in choroidal nevi and may correlate and possibly predict functional visual loss.
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http://dx.doi.org/10.1001/jamaophthalmol.2016.3633DOI Listing
November 2016

Progressive Scleral Necrosis following I-125 Plaque Radiotherapy for Ciliochoroidal Melanoma with Protruding Extraocular Mass.

Ocul Oncol Pathol 2016 Apr 20;2(3):136-9. Epub 2015 Nov 20.

Department of Ophthalmology, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA.

Purpose: The aim of this study was to describe the side effects of I-125 brachytherapy in the treatment of uveal melanoma.

Methods: This study was conducted as a case report.

Results: We report a case of scleral necrosis and protruding episcleral mass following the treatment of uveal melanoma with I-125 brachytherapy.

Conclusions: Scleral necrosis after plaque radiotherapy can clinically simulate tumor recurrence with extraocular extension. The management of uveal melanoma requires a careful clinical follow-up, weighing the implications of treatment morbidity and mortality.
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http://dx.doi.org/10.1159/000441660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4881265PMC
April 2016

Assessing Prognosis in Uveal Melanoma.

Authors:
Zelia M Correa

Cancer Control 2016 Apr;23(2):93-8

Department of Ophthalmology, University of Cincinnati, OH 45267, USA.

Background: Because uveal melanoma is the most common primary malignant intraocular tumor in adults and carries a significant risk of metastases, which are mostly unresponsive to available systemic therapy, researchers have been searching for prognostic indicators to identify patients at increased risk for developing such metastasis.

Methods: The purpose of this study is to describe recent advances in prognostic testing of patients with uveal melanoma and the impact of these advances on the management of uveal melanoma. The relevant, peerreviewed literature as extracted and then further reviewed for scientific content.

Results: Demographic characteristics, clinical, and histopathological features alone are inadequate for predicting metastatic risk in individual patients with uveal melanoma. Some research has shown that cytogenetic abnormalities and principally transcriptomic features of tumor cells can independently predict high risk for uveal melanoma metastatic spread. Gene expression profiling of uveal melanoma cells may be accurate and biologically informative for molecular prognostication. Methods for detecting chromosomal gains and losses have predictive value but require additional clinical and cytological information. The latest step in the evolution of molecular testing has been the discovery of major driver mutations for possible use in targeted therapy.

Conclusions: Assay validation, quality control, and interpretation of results are essential for the reliability and reproducibility of these tests. Although these prognostic tests have improved the ability to identify patients at increased risk for developing metastasis, their use has not changed the management of uveal melanoma. However, genomic, analytical, and sequencing technologies will provide a critical step toward useful targeted therapies for patients with high-risk uveal melanoma.
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http://dx.doi.org/10.1177/107327481602300202DOI Listing
April 2016

Ultrasonographical assessment of implanted biodegradable device for long-term slow release of methotrexate into the vitreous.

Exp Eye Res 2016 07 12;148:30-32. Epub 2016 May 12.

Department of Ophthalmology, College of Medicine, University of Cincinnati, Cincinnati, OH, USA. Electronic address:

Our group has developed a biodegradable drug delivery device (micro-implant) for long-term slow intraocular release of methotrexate (MTX) that can be implanted in the peripheral vitreous. The purpose of this study was to assess the position of the implanted devices and the status of the adjacent vitreous and peripheral retina over time using B-scan ocular ultrasonography (US). In each of the eight New Zealand rabbits used in this study, a chitosan (CS) and poly-lactic acid (PLA)-based micro-implant containing approximately 400 μg of MTX and a placebo micro-implant without MTX were inserted into the peripheral vitreous of the right and left eyes, respective, employing minimally invasive surgery. B-scan US imaging was performed on all of the rabbits immediately after implant insertion and on two rabbits at each of several pre-determined time points post-insertion (post-insertion days 5, 12, 19, and 33) to evaluate the position of the micro-implants and identify any evident morphological changes in the micro-implants and in the peripheral retina and vitreous during treatment. US imaging revealed stable positioning of the PLA-coated CS-based MTX micro-implant and the placebo micro-implant in the respective eyes throughout the study and lack of any changes in size, shape or sonoreflectivity of the micro-implants or abnormalities of the peripheral vitreous or retina in any of the study eyes. In summary, US did not show any evident morphological changes in the micro-implants, shifts in post-insertion position of the micro-implants, or identifiable changes in the micro-implants or peripheral vitreous and retina of the study eyes.
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http://dx.doi.org/10.1016/j.exer.2016.05.014DOI Listing
July 2016

Ocular Adnexal Lymphoma Presenting with Visual Loss.

N Am J Med Sci 2016 Jan;8(1):56-60

Chief, Hematological Malignancies and Bone Marrow Transplantation Program, University of Cincinnati Medical Center, Cincinnati, Ohio, USA.

Context: Elderly patients with visual loss often have age-related macular degeneration, diabetic retinopathy, glaucoma, and cataract as common causes of visual loss. Other less common etiologies should be considered, especially in those presenting with systemic associations.

Case Report: The patient discussed in our review is an 80-year-old female, with a history of diabetic retinopathy and macular degeneration who presented with a sudden deterioration of vision. While this was initially attributed to diabetic retinopathy, she was eventually noted to have a salmon patch lesion in her conjunctiva, diagnosed on biopsy to be a diffuse large B-cell lymphoma.

Conclusion: Because of the significant rate of disseminated disease among patients with lymphomas in the orbit that carries a worse prognosis, early diagnosis is essential to promote better overall survival of these patients. We describe here a patient diagnosed with conjunctival lymphoma associated with pronounced visual loss and review the literature on this subject.
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http://dx.doi.org/10.4103/1947-2714.175217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4784184PMC
January 2016

SUBRETINAL CANNULATION AS A COMPLICATION OF SUTURE TRABECULOTOMY SURGERY IN A PEDIATRIC PATIENT.

Retin Cases Brief Rep 2017 Winter;11(1):79-82

*College of Medicine, University of Cincinnati, Cincinnati, Ohio; †Cincinnati Eye Institute, Cincinnati, Ohio; ‡Department of Ophthalmology, Faculty of Medicine, Bahcesehir University, Istanbul, Turkey; and §Department of Ophthalmology, College of Medicine, University of Cincinnati, Cincinnati, Ohio.

Purpose: To report a case of inadvertent subretinal cannulation of ab externo suture trabeculotomy surgery associated with serous macular detachment.

Methods: Retrospective case report. Ophthalmic examination and portable spectral domain optical coherence tomography (Envisu C2300; Bioptogen, Morrisville, NC) were performed under general anesthesia.

Results: A 5-year-old girl with uveitis secondary to oligoarticular juvenile idiopathic arthritis underwent trabeculotomy surgery of the left eye for steroid-induced glaucoma refractory to medical management. The surgery was complicated by inadvertent subretinal cannulation with the prolene suture. Multiple, arcuate, hypopigmented subretinal tracks, originating from the ora serrata, were observed. Spectral domain optical coherence tomography images through the macula revealed subretinal fluid overlying funduscopically visible tracks, defects in photoreceptor outer segments overlying the tracks, and normal choroidal anatomy. The serous macular detachment resolved spontaneously after 4 months and visual acuity returned to baseline 20/25 in the left eye, consistent with reversible localized damage to the outer retina and retinal pigment epithelium.

Conclusion: We report a case of inadvertent subretinal cannulation during suture trabeculotomy surgery that resulted in serous macular detachment which resolved spontaneously. The inadvertent complication demonstrated a pathway for administration of therapeutics to the subretinal space.
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http://dx.doi.org/10.1097/ICB.0000000000000294DOI Listing
April 2017