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1. Declining incidence and improving survival of ocular and orbital lymphomas in the US between 1995 and 2018

Author: Ahmad Samir Alfaar, Yacoub A. Yousef, Matthew W. Wilson, Omneya Hassanain, Vinodh Kakkassery, Mohanad Moustafa, Ahmad Kunbaz, Amanne Esmael, and Olaf Strauß
Subjects: Ocular, Orbital, Lymphoma, Epidemiology, Incidence, Survival, Medicine, Science
Abstract: Abstract This epidemiological study examined ocular and orbital lymphomas in the United States from 1995 to 2018, using data from the North American Association of Central Cancer Registries database of 87,543 patients with ocular and adnexal malignancies. We identified 17,878 patients (20.4%) with ocular and orbital lymphomas, with an age-standardized incidence rate (ASIR) of 2.6 persons per million (ppm). The incidence was the highest in the orbit (ASIR = 1.24), followed by the conjunctiva (ASIR = 0.57). Non-Hodgkin B-cell lymphoma was the most prevalent subtype (85.4%), particularly marginal-zone lymphoma (45.7%). Racial disparities were noted, with Asia–Pacific Islanders showing the highest incidence (orbit, 1.3 ppm). The incidence increased significantly from 1995 to 2003 (Average Percent Change, APC = 2.1%) but declined thereafter until 2018 (APC = − 0.7%). 5-year relative survival (RS) rates varied, with the highest rate for conjunctival lymphoma (100%) and the lowest for intraocular lymphoma (70.6%). Survival rates have generally improved, with an annual increase in the 5-year RS of 0.45%. This study highlights the changing epidemiological landscape, pointing to initial increases and subsequent decreases in incidence until 2003, with survival improvements likely due to advancements in treatment. These findings underscore the need for further research to investigate the root causes of these shifts and the declining incidence of ocular lymphoma.
Published: 2024
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2. Retinoblastoma with and without Extraocular Tumor Extension

Author: Swathi Kaliki, MD, Vijitha S. Vempuluru, MD, Ido Didi Fabian, MD, Elhassan Abdallah, MD, Shehu U. Abdullahi, MD, Rula A. Abdulqader, MD, Aminatu A. Abdulrahaman, MD, Sherif Abouelnaga, MD, Dupe S. Ademola-Popoola, FMCOph, FWACS, Adedayo Adio, FWACS, Mahmoud A. Afifi, MD, Armin R. Afshar, MD, Priyanka Aggarwal, MD, Ada E. Aghaji, FMCOph MSc, Alia Ahmad, MRCPCH UK, Marliyanti N.R. Akib, MD, Adeseye M. Akinsete, MBBS, Lamis Al Harby, MD, Saleh A. Al Mesfer, MD, Mouroge H. Al Ani, MD, Silvia Alarcón Portabella, MD, Safaa A.F. Al-Badri, MD, Ana Patricia A. Alcasabas, MD, Saad A. Al-Dahmash, MD, Amanda Alejos, MD, Ernesto Alemany-Rubio, MD, Amadou I. Alfa Bio, MD, Yvania Alfonso Carreras, MD, Christiane E. Al-Haddad, MD, Hamoud H.Y. Al-Hussaini, MD, MSc, Amany M. Ali, MD, Donjeta B. Alia, MD, Mazin F. Al-Jadiry, MD, Usama Al-Jumaly, MD, Hind M. Alkatan, MD, Charlotta All-Eriksson, MD, PhD, Ali A.R.M. Al-Mafrachi, FIBMS, Argentino A. Almeida, MD, Khalifa M. Alsawidi, MD, Athar A.S.M. Al-Shaheen, MD, Entissar H. Al-Shammary, MD, Doreen Amankwaa-Frempong, MBChB, Primawita O. Amiruddin, MD, Inggar Armytasari, MD, Nicholas J. Astbury, FRCS, FRCOphth, Hatice T. Atalay, MD, Eda Ataseven, MD, La-ongsri Atchaneeyasakul, MD, Rose Atsiaya, OCO, Rudolf Autrata, MD, PhD, Julia Balaguer, MD, PhD, Ruhengiz Balayeva, PhD, Honorio Barranco, MD, PhD, Paulina Bartoszek, MD, Katarina Bartuma, MD, PhD, Covadonga Bascaran, MD, MSc, Nikolaos E. Bechrakis, MD, Maja Beck Popovic, MD, Ainura S. Begimkulova, MD, Sarra Benmiloud, MD, Rokia C. Berete, MD, PhD, Jesse L. Berry, MD, Anirban Bhaduri, MD, Sunil Bhat, MBBS, MD, Arpita Bhattacharyya, MD, Eva M. Biewald, MD, Elaine Binkley, MD, Sharon Blum, MD, Nadia Bobrova, MD, H. Culver Boldt, MD, Maria Teresa B.C. Bonanomi, MD, PhD, Gabrielle C. Bouda, MD, Hédi Bouguila, MD, PhD, Rachel C. Brennan, MD, Bénédicte G. Brichard, MD, PhD, Jassada Buaboonnam, MD, Aléine Budiongo, MD, Matthew Burton, FRCOphth, Patricia Calderón-Sotelo, MD, Doris A. Calle Jara, MD, Jayne E. Camuglia, FRANZCO, Miriam R. Cano, MD, MSc, Michael Capra, FRCPI, Shani Caspi, MD, Nathalie Cassoux, MD, PhD, Guilherme Castela, MD, Luis Castillo, MD, Jaume Català-Mora, MD, PhD, Isabel Caviedes, MD, Arthika Chandramohan, MD, Guillermo L. Chantada, MD, PhD, Shabana Chaudhry, MD, Bhavna Chawla, MD, Wensi Chen, MD, Faraja S. Chiwanga, MSc, Tsengelmaa Chuluunbat, MD, PhD, Krzysztof Cieslik, MD, Antony Clark, FRANZCO, Ruellyn L. Cockcroft, MB ChB , M Med Paed, Codruta Comsa, MD, Maria G. Correa Llano, MD, Timothy W. Corson, PhD, Line Couitchere, MD, Kristin E. Cowan-Lyn, MD, MBBS, Monika Csóka, MD, PhD, Wantanee Dangboon, MD, Anirban Das, MD, Pranab Das, MD, Sima Das, MS, Jacquelyn M. Davanzo, BSN, BSPH, Alan Davidson, MBChB, MPhil, Sonia De Francesco, MD, Patrick De Potter, MD, PhD, Karina Q. Delgado, MD, PhD, Hakan Demirci, MD, Laurence Desjardins, MD, Rosdali Y. Diaz Coronado, MD, Helen Dimaras, PhD, Andrew J. Dodgshun, M Phil, Carla R. Donato Macedo, MD, Monica D. Dragomir, MD, PhD, Yi Du, MD, Magritha Du Bruyn, MD, Johannes P. Du Plessis, MMed (Paed), Gagan Dudeja, MBBS, MS, Katrin Eerme, MD, I Wayan Eka Sutyawan, MD, Asmaa El Kettani, MD, Amal M. Elbahi, MD, James E. Elder, MBBS, Alaa M. Elhaddad, MD, PhD, Moawia M.A. Elhassan, MD, Mahmoud M. Elzembely, MD, Connor Ericksen, MD, Vera A. Essuman, FWACS, Ted Grimbert A. Evina, MD, Ifeoma R. Ezegwui, FMCOph, FWACS, FAEH, Zehra Fadoo, MBBS, Adriana C. Fandiño, MD, Mohammad Faranoush, MD, Oluyemi Fasina, FWACS, Delia D.P.G. Fernández, MSc, Ana Fernández-Teijeiro, MD, PhD, Allen Foster, FRCOphth, Shahar Frenkel, MD, PhD, Ligia D. Fu, MD, Soad L. Fuentes-Alabi, MD, MPH, Juan L. Garcia, MSc, David García Aldana, MD, Henry N. Garcia Pacheco, MD, Jennifer A. Geel, MBChB, MMed, Fariba Ghassemi, MD, Ana V. Girón, MD, Marco A. Goenz, MD, Aaron S. Gold, OD, Hila Golberg, MD, Glen A. Gole, MD, FRANZCO, Nir Gomel, MD, Efren Gonzalez, MD, Graciela Gonzalez Perez, MD, Liudmira González-Rodríguez, MD, Malka Gorfine, PhD, Jaime Graells, MD, Pernille A. Gregersen, MD, Nathalia D.A.K. Grigorovski, MD, Koffi M. Guedenon, MD, D Sanjeeva Gunasekera, MD, Ahmet K. Gündüz, MD, Himika Gupta, MD, Sanjiv Gupta, MS, Vineeta Gupta, MD, Theodora Hadjistilianou, MD, Patrick Hamel, MD, Syed A. Hamid, FCPS, Norhafizah Hamzah, MSc, Eric D. Hansen, MD, J William Harbour, MD, M. Elizabeth Hartnett, MD, Murat Hasanreisoglu, MD, Sadiq Hassan, MD, FWACS, Shadab Hassan, FRCS, FCPS, Wojciech Hautz, MD, Huda A. Haydar, CHD, Stanislava Hederova, MD, Laila Hessissen, MD, Hoby Lalaina, MD, Suradej Hongeng, MD, Diriba F. Hordofa, MD, G. Baker Hubbard, MD, Marlies Hummlen, MD, Kristina Husakova, MD, Allawi N. Hussein Al-Janabi, MD, Affiong A. Ibanga, MB.BCh, FMCOph, Russo Ida, MD, Vesna R. Ilic, MD, Ziyavuddin Islamov, MD, Vivekaraj Jairaj, DNB, Teyyeb A. Janjua, MD, FCPS, FRCSEd, Irfan Jeeva, FRCOphth, Xunda Ji, MD, Dong Hyun Jo, MD, PhD, Michael M. Jones, MD, PhD, FRANZCO, Theophile B. Amani Kabesha, MD, PhD, Rolande L. Kabore, MD, Abubakar Kalinaki, MD, Pius Kamsang, MD, Mehmet Kantar, MD, Noa Kapelushnik, MD, Tamar Kardava, PhD, Rejin Kebudi, MD, Jonny Keomisy, MD, Tomas Kepak, MD, Petra Ketteler, MD, Zohora J. Khan, MD, Hussain A. Khaqan, MD, Vikas Khetan, FRCS, FACS, Alireza Khodabande, MD, Zaza Khotenashvili, MD, Jonathan W. Kim, MD, Jeong Hun Kim, MD, PhD, Hayyam Kiratli, MD, Tero T. Kivelä, MD, Artur Klett, MD, PhD, Irem Koç, MD, Jess Elio Kosh Komba Palet, MD, Dalia Krivaitiene, MD, PhD, Mariana Kruger, Mmed Paed, PhD, Kittisak Kulvichit, MD, Mayasari W. Kuntorini, MD, Alice Kyara, BA, Geoffrey C. Lam, FRANZCO, Scott A. Larson, MD, Slobodanka Latinović, MD, PhD, Kelly D. Laurenti, MD, Yotam Lavi, MD, PhD, Alenka Lavric Groznik, MD, Amy A. Leverant, MD, Cairui Li, MD, Kaijun Li, MD, Ben Limbu, MD, Chun-Hsiu Liu, MD, Quah Boon Long, FRCS (Ed), MMed ( Ophth), FAMS, Juan P. López, MD, Robert M. Lukamba, MD, Sandra Luna-Fineman, MD, Delfitri Lutfi, MD, Lesia Lysytsia, MD, Shiran Madgar, MD, George N. Magrath, MD, Amita Mahajan, MD, Puja Maitra, MD, Erika Maka, MD, Emil K. Makimbetov, MD, Azza M.Y. Maktabi, MD, Carlos Maldonado, MD, Ashwin Mallipatna, MD, Rebecca Manudhane, MD, Lyazat Manzhuova, MD, Nieves Martín Begue, MD, PhD, Sidra Masud, MBBS, Ibrahim O. Matende, MD, M. Med (Oph), Clarissa C.D.S. Mattosinho, MD, Marchelo Matua, BAPH, Ismail Mayet, MD, Freddy B. Mbumba, MD, MMed Paed, John D. McKenzie, MD, Azim Mehrvar, MD, Aemero A. Mengesha, MD, Vikas Menon, MD, Gary John V.D.D. Mercado, MD, Marilyn B. Mets, MD, Edoardo Midena, MD, PhD, Audra Miller, MD, Divyansh K.C. Mishra, DNB, Furahini G. Mndeme, MD, Ahmed A. Mohamedani, FRCPath, Mona T. Mohammad, MD, FRCS, Annette C. Moll, MD, PhD, Margarita M. Montero, MD, Claude Moreira, MD, PhD, Prithvi Mruthyunjaya, MD, MHS, Mchikirwa S. Msina, MMed Ophth, Gerald Msukwa, MMed Ophth, Sangeeta S. Mudaliar, DNB Pediatric, Hassan Muhammad, MD, Kangwa I. Muma, MMed Ophth, FCOphth, Francis L. Munier, MD, Timothy G. Murray, MD, MBA, Kareem O. Musa, FWACS, FMCOphth, FICO, Asma Mushtaq, MD, Anne A. Musika, MD, Hamzah Mustak, MD, Tajudeen Mustapha, MBBS, FWACS, Okwen M. Muyen, MD, Khumo H. Myezo, Msc, Gita Naidu, MMed Paed, PhD, Natasha Naidu, MBCHB, FCS Ophthalmol, Akshay Gopinathan Nair, MD, Sundaram Natarajan, FRCS, Larisa Naumenko, MD, PhD, Paule Aïda Ndoye Roth, MD PhD, Yetty M. Nency, MD, Vladimir Neroev, MD, PhD, Yvonne Ng, MBChB ( Auckland) , FRANZCO, Marina Nikitovic, MD, PhD, Elizabeth D. Nkanga, FMCOph, Henry E. Nkumbe, MD, Marcel N. Numbi, MD, Kalle Nummi, MD, Murtuza Nuruddin, FRCS, Mutale Nyaywa, MD, MMed Ophth, FCOphth, Chinsisi Nyirenda, MD, Ghislaine Obono-Obiang, MD, Scott C.N. Oliver, MD, Joaquin Ooporto, MD, Miriam Ortega-Hernández, MD, Alexander Oscar, MD, Diego Ossandon, MD, Halimah Pagarra, MD, PhD, Vivian Paintsil, FWACP, Luisa Paiva, MD, Mahesh Shanmugam Palanivelu, FRCSED, Ruzanna Papyan, MD, Raffaele Parrozzani, MD, PhD, Claudia R. Pascual Morales, MD, Katherine E. Paton, MD, FRCSC, Jacob Pe'er, MD, Jesús Peralta Calvo, MD, Sanja Perić, MD, PhD, Chau T.M. Pham, MD, Remezo Philbert, MD, David A. Plager, MD, Pavel Pochop, MD, PhD, Rodrigo A. Polania, MD, Vladimir Polyakov, MD, Jimena Ponce, MD, Ali O. Qadir, MD, Seema Qayyum, FCPS, Jiang Qian, MD, Ardizal Rahman, MD, Purnima Rajkarnikar, MD, Rajesh Ramanjulu, MD, Aparna Ramasubramanian, MD, Marco A. Ramirez-Ortiz, MD, MPH, Jasmeen K. Randhawa, BA, Léa Raobela, MD, Riffat Rashid, MS, M. Ashwin Reddy, FRCOphth, Lorna A. Renner, FRCPCH (UK), David Reynders, MD, Dahiru Ribadu, FMCOph, Petra Ritter-Sovinz, MD, Anna Rogowska, MD, Duangnate Rojanaporn, MD, Livia Romero, MD, Soma R. Roy, DCO, Raya H. Saab, MD, Svetlana Saakyan, MD, PhD, Ahmed H. Sabhan, MD, Mandeep S. Sagoo, FRCS (Ed), Azza M.A. Said, MD, Rohit Saiju, MD, Beatriz Salas, MD, Sonsoles San Román Pacheco, MD, Gissela L. Sánchez, MD, Alma Janeth Sanchez Orozco, MD, Phayvanh Sayalith, MD, Trish A. Scanlan, MRCPI, MSc, Christoph Schwab, MD, Ahad Sedaghat, MD, Rachna Seth, DNB MNAMS, Mariana Sgroi, MD, Ankoor S. Shah, MD, PhD, Shawkat A. Shakoor, MS, Manoj K. Sharma, MD, Sadik T. Sherief, MD, Carol L. Shields, MD, David Sia, MB ChB, FRANZCO, Sorath Noorani Siddiqui, MD, Sidi Sidi cheikh, MD, PhD, Sónia Silva, MD, Arun D. Singh, MD, Usha Singh, MS, Penny Singha, MD, Rita S. Sitorus, MD, PhD, Alison H. Skalet, MD, PhD, Hendrian D. Soebagjo, MD, PhD, Tetyana Sorochynska, MD, PhD, Grace Ssali, MD, Andrew W. Stacey, MD, Sandra E. Staffieri, PhD, Erin D. Stahl, MD, David M. Steinberg, PhD, David K. Stones, MBChB, FCPaed, Caron Strahlendorf, MD, Maria Estela Coleoni Suarez, MD, Sadia Sultana, FCPS, Xiantao Sun, MD, Rosanne Superstein, MD, Eddy Supriyadi, MD, PhD, Supawan Surukrattanaskul, MD, Shigenobu Suzuki, MD, PhD, Karel Svojgr, MD, PhD, Fatoumata Sylla, MD, Gevorg Tamamyan, MD, PhD, Deborah Tan, MBBS, Alketa Tandili, MD, PhD, Jing Tang, MD, Fanny F. Tarrillo Leiva, MD, Maryam Tashvighi, MD, Bekim Tateshi, MD, PhD, Kok Hoi Teh, MD, Edi S. Tehuteru, MD, Luiz F. Teixeira, MD, Manca Tekavcic Pompe, MD, PhD, Abdullah Dahan M. Thawaba, MD, Tuyisabe Theophile, MSc, Helen Toledano, MBChB, Doan L. Trang, MD, Fousseyni Traoré, MD, Devjyoti Tripathy, MD, Samuray Tuncer, MD, Harba Tyau-Tyau, MD, Ali B. Umar, MD, FMCPath, Emel Unal, MD, Ogul E. Uner, BA, Steen F. Urbak, MD, PhD, Tatiana L. Ushakova, MD, Rustam H. Usmanov, MD, Sandra Valeina, MD, Paola Valente, MD, Milo van Hoefen Wijsard, MD, Jacqueline Karina Vasquez Anchaya, MD, Leon O. Vaughan, FRCS (Ed), Nevyana V. Veleva-Krasteva, MD, PhD, Nishant Verma, MD, Andi A. Victor, MD, PhD, Maris Viksnins, MD, Edwin G. Villacís Chafla, MD, Victor M. Villegas, MD, Victoria Vishnevskia-Dai, MD, Keith Waddell, DM, FRCP, FRCS, FRCOphth, Amina H. Wali, MD, FMCOph Nigeria, Yi-Zhuo Wang, MD, Nutsuchar Wangtiraumnuay, MD, FICO, Julie A. Wetter, MMed Rad Onc, FCRad Onc, Widiarti P. Riono, MD, Matthew W. Wilson, MD, Amelia D.C. Wime, MD, Atchareeya Wiwatwongwana, MD, Damrong Wiwatwongwana, MD, Charlotte Wolley Dod, MD, Emily S. Wong, FCOphth HK, FHKAM, Phanthipha Wongwai, MD, PhD, Si-qi Wu, MSc, Daoman Xiang, MD, PhD, Yishuang Xiao, MSc, Bing Xu, MD, Kang Xue, MD, Antonio Yaghy, MD, Jason C. Yam, FRCSEd, Huasheng Yang, MD, Jenny M. Yanga, MD, Muhammad A. Yaqub, MD, FCPS, FRCSEd, Vera A. Yarovaya, MD, Andrey A. Yarovoy, MD, PhD, Huijing Ye, MD, Roberto I. Yee, MD, Yacoub A. Yousef, MD, Putu Yuliawati, MD, Arturo M. López, MD, Ekhtelbenina Zein, MD, Yi Zhang, MD, PhD, Katsiaryna Zhilyaeva, MD, Nida Zia, MBBS, MCPS, Othman A.O. Ziko, MD, PhD, Marcia Zondervan, MBA, Sabrina Schlüter, MD, and Richard Bowman, FRCOphth
Subjects: External beam radiotherapy, Extraocular extension, Multimodal treatment, Retinoblastoma, Tumor, Ophthalmology, RE1-994
Abstract: Purpose: To study the treatment and outcomes of children with retinoblastoma (RB) with extraocular tumor extension (RB-EOE) and compare them with RB without extraocular tumor extension (RB-w/o-EOE). Design: Multicenter intercontinental collaborative prospective study from 2017 to 2020. RB-EOE cases included those with overt orbital tumor extension in treatment-naive patients. Cases with microscopic orbital extension detected postenucleation were excluded from the study. Participants: A total of 319 children with RB-EOE and 3116 children with RB-w/o-EOE. Intervention: Chemotherapy, enucleation, exenteration, radiotherapy. Main Outcome Measures: Systemic metastasis and death. Results: Of the 3435 RB patients included in this study, 309 (9%) were from low-income countries (LIC), 1448 (42%) from lower-middle income, 1012 (29%) from upper-middle income, and 666 (19%) patients from high-income countries. There was an inverse relationship between the percentage of RB-EOE and national income level, with 96 (31%) patients from LIC, 197 (6%) lower-middle income, 20 (2%) upper-middle income, and 6 (1%) patients from high-income countries (P = 0.0001). The outcomes were statistically significant for RB-EOE compared with RB-w/o-EOE: systemic metastasis (32% vs. 4% respectively; P = 0.0001) and metastasis-related death (63% vs. 6% respectively; P = 0.0001). Multimodal treatment was the most common form of treatment (n = 177; 54%) for RB-EOE, with most cases undergoing a combination of intravenous chemotherapy and enucleation (n = 97; 30%). Adjuvant external beam radiotherapy (EBRT) after surgery (enucleation/orbital exenteration) was given in only 68 (21%) cases. Kaplan–Meier analysis for systemic metastasis and metastasis-related death in RB-EOE was 28% and 57% at 1 year, 29% and 60% at 2 years, and 29% and 61% at 3 years, respectively. Cox regression analysis revealed that the risk of death from RB-EOE was greater in patients aged >4 years than
Published: 2025
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3. Mutational analysis of the RB1 gene in patients with unilateral retinoblastoma

Author: Yacoub A. Yousef, Mona Mohammad, Laith Baqain, Maysa Al-Hussaini, Mayada Abu Shanap, Hadeel Halalsheh, Jakub Khzouz, Imad Jaradat, Mustafa Mehyar, Iyad Sultan, Ibrahim AlNawaiseh, and Munir Shawagfeh
Subjects: germline mutation, inherited disease, RB1 gene, retinoblastoma, unilateral, Medicine (General), R5-920
Abstract: PurposeRetinoblastoma, a childhood cancer originating in the retina, is primarily attributed to pathogenic RB1 mutations The aim of this study is to conduct a mutational analysis of the RB1 gene in cases of unilateral Retinoblastoma among individuals within the Jordanian population.MethodsIn this study, the peripheral blood of 50 unilateral Rb patients was collected, genomic DNA was extracted, and mutations were identified using Next Generation Sequencing (NGS) analysis.ResultsIn this cohort of 50 unrelated patients with unilateral Rb, the median age at diagnosis was eight months (mean, 12 months; range; 2 weeks to 54 months). Twenty-eight (56%) were males, 29 (58%) had the disease in the right eye, 3 (6%) had a positive family history of Rb, and 20 (40%) were diagnosed within the first year of life. RB1 gene pathogenic mutations were detected in 14 out of 50 (28%) patients, indicating germline disease. Among unilateral non-familial cases, 11 out of 47 (23%) were found to have germline RB1 mutations. Overall, five (36%) of the germline cases had the same mutation detected in one of the parents consistent with an inherited disease (four (80%) were of paternal origin); 3 (60%) of these had affected carrier parent, two (40%) had an unaffected carrier parent. Nine (64%) patients had the nonsense mutation, and six (43%) had the mosaic mutation. The significant prognostic factors for positive genetic testing were positive family history (p = 0.018) and age at diagnosis less than 12 months (p = 0.03). At a median of 54 months follow-up, two (4%) patients were dead from distant metastasis. The overall eye salvage rate was 44% (n = 22/50) eyes; 100% for groups A, B, and C, 60% for group D, and none for group E eyes. There was no correlation between the presence of germline mutation and outcome in terms of eye salvage, metastasis, and survival.ConclusionIn this study, 28% of patients with unilateral Rb had germline RB1 mutations, of which 43% were inherited, and one-third presented beyond their first year of life. Therefore, molecular screening is critical for genetic counseling regarding the risk for inherited Rb in unilateral cases, including those with no family history, regardless of the age at diagnosis. However, germline mutations did not appear to significantly predict patient outcomes regarding eye salvage, metastasis, and survival.
Published: 2024
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4. From Molecular Biology to Novel Immunotherapies and Nanomedicine in Uveal Melanoma

Author: Kamil J. Synoradzki, Natalia Paduszyńska, Malgorzata Solnik, Mario Damiano Toro, Krzysztof Bilmin, Elżbieta Bylina, Piotr Rutkowski, Yacoub A. Yousef, Claudio Bucolo, Sandrine Anne Zweifel, Michele Reibaldi, Michal Fiedorowicz, and Anna M. Czarnecka
Subjects: uveal melanoma, biomarkers, immunotherapy, theranostics, nanomedicine, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Molecular biology studies of uveal melanoma have resulted in the development of novel immunotherapy approaches including tebentafusp—a T cell–redirecting bispecific fusion protein. More biomarkers are currently being studied. As a result, combined immunotherapy is being developed as well as immunotherapy with bifunctional checkpoint inhibitory T cell engagers and natural killer cells. Current trials cover tumor-infiltrating lymphocytes (TIL), vaccination with IKKb-matured dendritic cells, or autologous dendritic cells loaded with autologous tumor RNA. Another potential approach to treat UM could be based on T cell receptor engineering rather than antibody modification. Immune-mobilizing monoclonal T cell receptors (TCR) against cancer, called ImmTAC TM molecules, represent such an approach. Moreover, nanomedicine, especially miRNA approaches, are promising for future trials. Finally, theranostic radiopharmaceuticals enabling diagnosis and therapy with the same molecule bring hope to this research.
Published: 2024
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5. Causes of death and survival analysis for patients with retinoblastoma in Jordan

Author: Tharwa Bilbeisi, Razaq Almasry, Mariam Obeidat, Mona Mohammad, Imad Jaradat, Hadeel Halalsheh, Ayat Alni’mat, Danah Kanj Ahmad, Nour Alsaket, Mustafa Mehyar, Ibrahim Al-Nawaiseh, and Yacoub A. Yousef
Subjects: death, Jordan, metastasis, retinoblastoma, survival, Medicine (General), R5-920
Abstract: PurposeTo analyze causes and prognostic factors for death among Retinoblastoma (Rb) patients treated at a single specialized tertiary cancer center in Jordan.MethodsWe reviewed the mortality causes for all Rb patients who have been treated at the King Hussein Cancer Center between 2003 and 2019 and were followed for at least 3 years after diagnosis. The main outcome measures included demographics, laterality, tumor stage, treatment modalities, metastasis, survival, and causes of death.ResultsTwenty-four (5%) of the 478 patients died from retinoblastoma and 5-year survival was 94%. The mean age at diagnosis was 15 months (median, 18 months; range, 4–38 months); eight (33%) received diagnoses within the first year of life. Eleven (46%) were boys, 16 (67%) had bilateral disease, and 3 (13%) had a positive family history. The stage for the worst eye was C for 1 (4%) patient, D in 6 (25%) patients, and E (T3) in 15 (63%) patients. Two patients had extraocular Rb at diagnosis, and four of the patients who had intraocular Rb at diagnosis refused treatment and then came back with extraocular Rb. In total, extraocular disease was encountered in six eyes (six patients). After a 120-month median follow-up period, 24 patients (5%) died of second neoplasms (n = 3) or metastases (n = 21). Significant predictive factors for metastasis and death included advanced IIRC tumor stage (p
Published: 2023
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6. Presentation and management outcomes of Retinoblastoma among Syrian refugees in Jordan

Author: Yacoub A. Yousef, Qusai F. Abu Salim, Mona Mohammad, Imad Jaradat, Mustafa Mehyar, Reem AlJabari, Omar Al-Habahbeh, Khalid Saboubeh, Hadeel Halalsheh, Jakub Khzouz, Munir Shawagfeh, Iyad Sultan, Mahmoud AlMasri, Ibrahim Al-Nawaiseh, Maysa Al-Hussaini, and Asem Mansour
Subjects: enucleation, eye salvage, refugees, Retinoblastoma, survival, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: PurposeThe humanitarian crisis in Syria has had a profound impact on the entire region. In this study, we report the patterns of presentation and management outcomes of Syrian patients with Retinoblastoma (Rb) treated at a single tertiary cancer center in Jordan.Methods and MaterialsThis is a retrospective comparative study of Syrian refugees and Jordanian citizens who had Rb between 2011 and 2020. Collected data included patient demographics, presentation, tumor stage, treatment modalities, eye salvage rate, metastasis, and mortality.ResultsThirty Syrian refugees (16 (53%) had bilateral disease) and 124 Jordanian citizens (51(41%) had bilateral disease) were diagnosed with Rb during this period. The median age at diagnosis for refugees was 10 and 32 months for patients with bilateral and unilateral Rb consecutively, compared to 6 and 28 months for citizens. The median lag time between signs of disease and initiation of treatment was 3 months for refugees, compared to 1 month for citizens.Refugees were more likely to present with a more advanced stage (p=0.046). Out of 46 affected eyes in refugees; 32 (70%) eyes were group D or E, while out of 175 affected eyes among citizens; 98 (56%) eyes were group D or E. Therefore, refugees with Rb were more likely to mandate primary enucleation (48%) compared to citizens (25%) (p=0.003). However, out of 24 eyes among refugees who received conservative therapy, 15 (62%) eyes were successfully salvaged, while out of 131 affected eyes among citizens who received conservative therapy, 105 (80%) eyes were successfully salvaged (p=0.06). Two (7%) of the refugees and four (3.2%) of the citizens with Rb died from metastasis.ConclusionSyrian refugees with Rb presented with more advanced disease due to delay in diagnosis and referral that increased the treatment burden by decreasing the chance for eye globe salvage. However, patients who received the timely intervention had a similar outcome to citizens with Rb; probably a reflection of the management of all patients at a single specialized center. We advocate for the timely referral of refugees with this rare life-threatening tumor to a specialized cancer center for the best possible outcome.
Published: 2023
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7. Safety and Efficacy of Intravitreal Chemotherapy (Melphalan) to Treat Vitreous Seeds in Retinoblastoma

Author: Yacoub A. Yousef, Mays Al Jboor, Mona Mohammad, Mustafa Mehyar, Mario D. Toro, Rashed Nazzal, Qusai H. Alzureikat, Magdalena Rejdak, Mutasem Elfalah, Iyad Sultan, Robert Rejdak, Maysa Al-Hussaini, and Ibrahim Al-Nawaiseh
Subjects: chemotherapy, melphalan, ocular toxicity, retinoblastoma, vitreous seeds, Therapeutics. Pharmacology, RM1-950
Abstract: Background: Active vitreous seeds in eyes with retinoblastoma (Rb) adversely affects the treatment outcome. This study aimed to investigate the safety and efficacy of intravitreal melphalan chemotherapy (IViC) as a treatment for recurrent and refractory vitreous seeds in patients with Rb.Methods: We used a retrospective non-comparative study of patients with intraocular Rb who had vitreous seeds and were treated by IViC (20–30 μg of melphalan) using the safety-enhanced anti-reflux technique. Tumor response, ocular toxicity, demographics, clinical features, and survival were analyzed.Results: In total, 27 eyes were treated with 108 injections for recurrent (16 eyes) or refractory (11 eyes) vitreous seeds after failed systemic chemotherapy. A total of 15 (56%) were males, and 20 (74%) had bilateral disease. At diagnosis, the majority (n = 21) of the injected eyes were group D, and n = 6 were group C. Vitreous seeds showed complete regression in 21 (78%) eyes; 100% (n = 10) for eyes with focal seeds; 65% (n = 11/17 eyes) for eyes with diffuse seeds (p = 0.04); 7 (64%) eyes with refractory seeds; and 14 (87%) eyes with recurrent seeds showed complete response (p = 0.37). In total, 16 (59%) eyes developed side effects: retinal toxicity (48%), pupillary synechiae (15%), cataracts (30%), iris atrophy (7%), and retinal and optic atrophy (4%). Only one child was lost to follow-up whose family refused enucleation and none developed orbital tumor recurrence or distant metastasis.Conclusion: IViC with melphalan is effective (more for focal than diffuse seeding) and a relatively safe treatment modality for Rb that can improve the outcomes of eye salvage procedures. However, unexpected toxicity can occur even with the standard dose of 20–30 μg.
Published: 2021
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8. Concomitant Intraocular Retinoblastoma and Choroidal Hemangioma in a 1-Year-Old Boy

Author: Yacoub A. YOUSEF, Maysa AL-HUSSAİNİ, Fareed H. BARAKAT, Alaa SALEH, Mona MOHAMMAD, and Rasha DEEBAJAH
Subjects: Choroidal neoplasm, Hemangioma, Leukocoria, Retinoblastoma, Pathology, RB1-214
Abstract: We report a case of concomitant choroidal hemangioma in an eye that harbored intraocular retinoblastoma (RB) in a 1-year-old child. A 12-month-old boy presented with right white pupil (Leukocoria). The initial clinical diagnosis was unilateral intraocular RB Group C. The eye was treated initially by systemic chemotherapy combined with focal consolidation therapy followed by I-125 plaque radiotherapy. Massive sub-retinal recurrence was seen 4 months later, and Magnetic Resonance Imaging (MRI) showed extra-scleral invasion of the tumor, and therefore enucleation was performed. Microscopic examination revealed a differentiated retinoblastoma associated at the site of the base of the tumor with choroidal hemangioma with trans-scleral invasion. Orbit MRI was repeated 3 months after the surgery, and there was no orbital tumor recurrence. We are reporting a rare case of pathologically concomitant choroidal hemangioma with trans-scleral invasion in an eye that harbored active recurrent intraocular RB. This trans-scleral extension of hemangioma was misinterpreted by MRI as extraocular retinoblastoma and resulted in enucleation.
Published: 2019
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9. Intravitreal Melphalan Chemotherapy for Vitreous Seeds in Retinoblastoma

Author: Yacoub A. Yousef, Amal M. Noureldin, Iyad Sultan, Rasha Deebajah, Maysa Al-Hussaini, Munir Shawagfeh, Mustafa Mehyar, Mona Mohammad, Imad Jaradat, and Ibrahim AlNawaiseh
Subjects: Ophthalmology, RE1-994
Abstract: Objective. To evaluate our experience with intravitreal melphalan chemotherapy as a second-line regimen for RB patients with refractory or recurrent vitreous seeds. Methods. A retrospective case series of 16 eyes from 16 patients with intraocular RB who received intravitreal melphalan chemotherapy using the antireflux injection technique. Data included demographics, stage at diagnosis, treatment modalities, side effects, eye salvage, and survival. Results. The total number of injections was 64 (median, 3 injections per eye; range, 3–8), and the median age at time of injection was 22 months (range, 9–63 months). Nine (56%) patients were males, and 13 (81%) patients had bilateral RB. Complete response was seen in 13 (81%) eyes: in 9 (100%) eyes with focal vitreous seeds and in 4 (57%) eyes with diffuse vitreous seeds (P=0.062). At a median follow-up of 18 months (range, 6–48 months), the eye salvage rate was 81%, local retinal toxicity confined to the site of injection was seen in 2/3 of the eyes, 2 (12%) eyes had cataract, and none of the patients had orbital recurrence and distant metastasis or was dead. Conclusion. Intravitreal melphalan is a promising modality for treatment of vitreous seeds, and the dose of 20–30 μg of melphalan sounds to be safe and effective for refractory and recurrent vitreous seeds.
Published: 2020
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10. Characteristics, management, and outcome of squamous carcinoma of the conjunctiva in a single tertiary cancer center in Jordan

Author: Ata Rajeh, Fareed Barakat, Samer Khurma, Khaleel AlRawashdeh, Osama H. Ababneh, Ibrahim AlNawaiseh, Mustafa Mehyar, Ghadeer Abdeen, Imad Jaradat, Mona Mohammad, and Yacoub A. Yousef
Subjects: 1138, conjunctiva, squamous cell carcinoma, metastasis, Ophthalmology, RE1-994
Abstract: AIM: To evaluate the features and outcome of management of malignant conjunctival squamous tumors in King Hussein Cancer Center (a referral tertiary cancer center in the Middle East). METHODS: Retrospective case series of 31 eyes for 31 patients with conjunctival squamous neoplasia. Main outcome measures included: age, gender, laterality, tumor location, pathological features, tumor stage, treatment modality, and outcome. RESULTS: Twenty (65%) patients were males and median age was 58y. Twenty-two (71%) eyes had the tumor in the nasal quadrant. Tumor invasion to nearby structures was seen in 19 (61%) eyes, including the cornea, fornix, eyelid, and orbit in 17 (55%), 1 (3%), 2 (6%), and 3 (10%) eyes, respectively. Eye salvage was achieved by surgical excision with cryotherapy followed by topical chemotherapy in 28 (90%) eyes, and orbital exenteration was necessary in 3 (10%) eyes due to orbital tumor invasion. Tumor recurrence was seen in 7 (23%) eyes, and the significant predictive factors for recurrence were tumor extension onto the nearby structures (P=0.04), tumor invasiveness (P=0.038), and tumor TNM stage (P=0.031). No significant change in visual acuity was seen, and disease related mortality was 6% (2 patients, both had orbital invasion by invasive squamous carcinoma). CONCLUSION: Conjunctival squamous carcinoma is more common in males. Advanced American Joint Committee on Cancer (AJCC) T-stage, tumor local invasion, more pathologically aggressive tumors, and surgical treatment alone (without adjuvant therapy) are associated with higher risk for recurrence, and orbital invasion is the most important poor prognostic factor for metastasis and death. Treatment strategies should be affected by tumor characteristics at presentation.
Published: 2018
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11. New Therapeutic Perspectives in the Treatment of Uveal Melanoma: A Systematic Review

Author: Mario Damiano Toro, Lucia Gozzo, Luciano Tracia, Marco Cicciù, Filippo Drago, Claudio Bucolo, Teresio Avitabile, Robert Rejdak, Katarzyna Nowomiejska, Sandrine Zweifel, Yacoub A. Yousef, Rashed Nazzal, and Giovanni Luca Romano
Subjects: uveal melanoma, treatment strategies, pharmacological treatment, local treatment, systemic treatment, Biology (General), QH301-705.5
Abstract: Uveal melanoma (UM) is a rare disease, but the most common primary intraocular cancer, mostly localized in the choroid. Currently, the first-line treatment options for UM are radiation therapy, resection, and enucleation. However, although these treatments could potentially be curative, half of all patients will develop metastatic disease, whose prognosis is still poor. Indeed, effective therapeutic options for patients with advanced or metastatic disease are still lacking. Recently, the development of new treatment modalities with a lower incidence of adverse events, a better disease control rate, and new therapeutic approaches, have merged as new potential and promising therapeutic strategies. Additionally, several clinical trials are ongoing to find new therapeutic options, mainly for those with metastatic disease. Many interventions are still in the preliminary phases of clinical development, being investigated in phase I trial or phase I/II. The success of these trials could be crucial for changing the prognosis of patients with advanced/metastatic UM. In this systematic review, we analyzed all emerging and available literature on the new perspectives in the treatment of UM and patient outcomes; furthermore, their current limitations and more common adverse events are summarized.
Published: 2021
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12. Familial Retinoblastoma: Raised Awareness Improves Early Diagnosis and Outcome

Author: Ibrahim Al-Nawaiseh, Aseel Q. Ghanem, and Yacoub A. Yousef
Subjects: Ophthalmology, RE1-994
Abstract: Purpose. To study the impact of awareness of retinoblastoma in the affected families on the management and outcome of familial retinoblastoma patients. Methods and Materials. This is a retrospective, clinical case series of 44 patients with familial retinoblastoma. Collected data included patient’s demographics, laterality, family history, age at diagnosis, presenting signs, treatment modalities, tumor stage, eye salvage rate, metastasis, and mortality. Results. Out of 200 retinoblastoma patients in our registry, 44 (22%) patients were familial, 18 were probands, and 26 were second, third, or fourth affected family members. There were 76 affected eyes: 31 eyes of probands and 45 eyes of the other affected family members. Among probands, all patients (100%) had at least one eye enucleated: 58% (18 eyes) of the affected eyes were enucleated and 32% (10 eyes) of the affected eyes were radiated. On the other hand, among the nonprobands, only 20% had one eye enucleated, and only 4 eyes (9%) received radiation. The eye salvage rate was significantly higher in the nonprobands than in the probands in this series (p=0.00206). Patients diagnosed by screening (38%) had excellent visual outcome, and both eyes were salvaged. Conclusion. Awareness of families of the possibility of retinoblastoma and adequate screening led to a significantly higher rate of eye salvage in patients with familial retinoblastoma.
Published: 2017
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13. High-risk Pathologic Features Based on Presenting Findings in Advanced Intraocular Retinoblastoma

Author: Ankit Singh Tomar, Paul T. Finger, Brenda Gallie, Tero T. Kivelä, Ashwin Mallipatna, Chengyue Zhang, Junyang Zhao, Matthew W. Wilson, Rachel C. Brennan, Michala Burges, Jonathan Kim, Jesse L. Berry, Rima Jubran, Vikas Khetan, Suganeswari Ganesan, Andrey Yarovoy, Vera Yarovaya, Elena Kotova, Denis Volodin, Yacoub A. Yousef, Kalle Nummi, Tatiana L. Ushakova, Olga V. Yugay, Vladimir G. Polyakov, Marco A. Ramirez-Ortiz, Elizabeth Esparza-Aguiar, Guillermo Chantada, Paula Schaiquevich, Adriana Fandino, Jason C. Yam, Winnie W. Lau, Carol P. Lam, Phillipa Sharwood, Sonia Moorthy, Quah Boon Long, Vera Adobea Essuman, Lorna A. Renner, Ekaterina Semenova, Jaume Català-Mora, Genoveva Correa-Llano, and Elisa Carreras
Subjects: Ophthalmology
Published: 2022
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14. Metastatic Death Based on Presenting Features and Treatment for Advanced Intraocular Retinoblastoma

Author: Ankit Singh Tomar, Paul T. Finger, Brenda Gallie, Tero T. Kivelä, Ashwin Mallipatna, Chengyue Zhang, Junyang Zhao, Matthew W. Wilson, Rachel C. Brennan, Michala Burges, Jonathan Kim, Jesse L. Berry, Rima Jubran, Vikas Khetan, Suganeswari Ganesan, Andrey Yarovoy, Vera Yarovaya, Elena Kotova, Denis Volodin, Yacoub A. Yousef, Kalle Nummi, Tatiana L. Ushakova, Olga V. Yugay, Vladimir G. Polyakov, Marco A. Ramirez-Ortiz, Elizabeth Esparza-Aguiar, Guillermo Chantada, Paula Schaiquevich, Adriana Fandino, Jason C. Yam, Winnie W. Lau, Carol P. Lam, Phillipa Sharwood, Sonia Moorthy, Quah Boon Long, Vera Adobea Essuman, Lorna A. Renner, Ekaterina Semenova, Jaume Català-Mora, Genoveva Correa-Llano, and Elisa Carreras
Subjects: Ophthalmology
Published: 2022
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15. MP44-15 THE VALUE OF PROSTATE-SPECIFIC ANTIGEN DENSITY IN LONG-TERM PROSTATE CANCER-MORTALITY RISK PREDICTION

Author: Yacoub, Sara Yousef, primary, Lundgren, Per-Olof, additional, Kjellman, Anders, additional, and Gustafsson, Ove, additional
Published: 2023
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16. The Impact of Color Vision Deficiency on the Capability of Ophthalmologists to Diagnose Benign and Malignant Choroidal Tumors

Author: Mutasem Elfalah, Saif Aldeen AlRyalat, Nakhleh E. Abu-Yaghi, Mona Mohammad, Ibrahim AlNawiaseh, Deema Rayyan, Moath Albliwi, Mohammad Elfalah, Fawaz AlSarairah, and Yacoub A. Yousef
Subjects: color blindness, fundus, nevus, malignant, color vision deficiency, protanopia, deuteranopia, General Medicine
Abstract: Background: Color vision deficiency (CVD) is an under-reported problem among medical personnel, and its impact is still not well characterized. We aim to assess the impact of CVD among ophthalmologists on the accuracy of diagnosing different benign and malignant choroidal lesions. Methods: This is a cross-sectional study conducted on ophthalmologists. We used a web-based survey to collect responses through professional ophthalmology society social media. The survey included a set of five images for normal fundus, choroidal nevus, circumscribed choroidal hemangioma, choroidal metastasis, and choroidal melanoma, wherein each image simulated the three main types of CVD: protanopia, deuteranopia, and tritanopia, in addition to a non-simulated image. Results: Forty-one participants were included, with a mean age of 40 (±9.2) years. They were 28 (68%) men and 13 (32%) women. Participants showed significantly low accuracy for definite diagnosis for circumscribed choroidal hemangioma, nevus, melanoma, and metastasis when the images simulated protanopia and deuteranopia, but not tritanopia. Nevertheless, participants maintained the capability to recognize the nature of the lesions for both simulated and non-simulated images if they were benign or malignant, thereby ensuring immediate referral for specialized care. The exception was with simulated choroidal nevi images, wherein participants incorrectly assigned simulated protanopia and deuteranopia nevi images to malignant lesions. Conclusion: Protanopia and deuteranopia affected the accuracy of diagnosing several choroidal lesions; however, ophthalmologists with those two simulated CVDs were still able to discriminate between benign and malignant tumors.
Published: 2023
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17. Cytomegalovirus Retinitis in a Child with Acute Lymphoblastic Leukemia

Author: Entisar H. A. L. Shammary, Ali Abdul Razzaq Mahmood Al-Mafrachi, Yacoub A. Yousef, and Safa Faraj
Subjects: General Medicine
Abstract: BACKGROUND: Due to the reduced immune response following chemotherapy, cytomegalovirus (CMV) retinitis is the most prevalent opportunistic intraocular infection in HIV-infected adults. It can also affect children with acute lymphoblastic leukemia (ALL). CASE PRESENTATION: We describe an 11.5-year-old female who is undergoing maintenance chemotherapy for B-lineage ALL. She had vision loss in her right eye and began to have hazy vision in her left eye. Bilateral active retinitis lesions were discovered during the retinal examination. The diagnosis of bilateral CMVR was made based on clinical symptoms, retinal examination findings, and a blood sample for CMV DNA detection using the polymerase chain reaction (PCR) technique. She was given ganciclovir intravenously and intravitreally, followed by oral valganciclovir prophylaxis. Patients who received a solid organ or hematopoietic stem cell transplant were infected with CMVR, although patients with ALL who received less immunosuppressive chemotherapy were also affected (maintenance phase therapy). Intravenous and intravitreal ganciclovir injections are effective treatments, the patient had significant clinical improvement. CMV retinitis is frequent in children with ALL who are in the maintenance phase of the treatment. CONCLUSION: The importance of early detection and treatment cannot be overstated. CMV retinitis: Key prognostic variables. CMV retinitis should be considered as cause of blurred vision in patients with ALL.
Published: 2022
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18. Ultrasound Biomicroscopy Measurements of the Normal Thickness for the Ciliary Body and the Iris in a Middle East Population

Author: Yacoub A Yousef, Mona Mohammad, Ibrahim AlNawaiseh, Reem AlJabari, Mario Damiano Toro, Almutez Gharaibeh, Robert Rejdak, Katarzyna Nowomiejska, Sandrine Zweifel, Teresio Avitabile, Magdalena Rejdak, Rashed Nazzal, Yousef, Ya, Mohammad, M, Alnawaiseh, I, Aljabari, R, Toro, Md, Gharaibeh, A, Rejdak, R, Nowomiejska, K, Zweifel, S, Avitabile, T, Rejdak, M, and Nazzal, R
Subjects: Ophthalmology, Iri, ciliary body, Clinical Ophthalmology, RE1-994, ultrasound biomicroscopy, Original Research, iris
Abstract: Yacoub A Yousef,1 Mona Mohammad,1 Ibrahim AlNawaiseh,1 Reem AlJabari,1 Mario Damiano Toro,2,3 Almutez Gharaibeh,4 Robert Rejdak,5 Katarzyna Nowomiejska,5 Sandrine Zweifel,3 Teresio Avitabile,6 Magdalena Rejdak,6 Rashed Nazzal2 1Department of Surgery (Ophthalmology), King Hussein Cancer Centre, Amman, Jordan; 2Faculty of Medical Sciences, Collegium Medicum, Cardinal Stefan Wyszy&nacute;ski University, Warsaw, Poland; 3Department of Ophthalmology, University of ZÃ¼rich, ZÃ¼rich, Switzerland; 4School of Medicine, The University of Jordan, Amman, Jordan; 5Department of General Ophthalmology, Medical University of Lublin, Lublin, Poland; 6Department of Ophthalmology, University of Catania, Catania, ItalyCorrespondence: Yacoub A YousefDepartment of Surgery (Ophthalmology), King Hussein Cancer Centre, Queen Rania St, Amman, 11941, JordanTel +96265355000Email yyousef@khcc.joMario Damiano ToroDepartment of Ophthalmology, University Hospital of ZÃ¼rich, Raemistrasse 100, ZÃ¼rich, 8091, SwitzerlandTel +39 3495158220Email toro.mario@email.itPurpose: Ciliary body (CB) and iris thicknesses may change with certain eye diseases as well as between different populations. Here, we report Ultrasound Biomicroscopy Measurements (UBM) of the normal thickness for the CB and the iris from a homogenous population in the Middle East.Patients and Methods: Sonomed 35-MHz (SONOMED, INC. New York, USA) images were obtained at 4 radial meridians, and the thickness was measured at 3 locations along the radial length of the iris and at the thickest part of the CB. Parameters included mean thickness, median thickness, range, and standard deviation.Results: Of 46 adult patients, 83 normal eyes were included in this analysis. The overall mean, median iris thicknesses at the iris root, midway along the radial length of the iris, and at the juxtapupillary margin in mm were 0.42, 0.41 Â± 0.08, 0.52, 0.51Â± 0.08, and 0.72, 0.71Â± 0.1, respectively. The overall mean, median thicknesses of the CB and CB + ciliary processes in mm were 0.72, 0.71 Â± 0.1, and 1.42, 1.37 Â± 0.2 respectively. Gender, age, side, and height had no impact on iris and/or CB thickness (p> 0.05). However, the iris thickness was significantly thicker in the superior quadrant than inferiorly, and in the nasal quadrant than the temporal quadrant (p=0.04), and the CB thickness and the CB + ciliary processes thickness were significantly thicker in the superior quadrant than inferiorly (P = 0.04 and 0.02 consecutively).Conclusion: We measured in this study the normal thickness of the CB and the iris in normal eyes from homogenous population in the Middle East using ultrasound biomicroscopy. Our findings are essential for the ophthalmic community worldwide and in the Middle East region and can be used as a normative thickness data for the iris and CB in healthy eyes.Keywords: ultrasound biomicroscopy, iris, ciliary body
Published: 2022

19. Reply

Author: Paul T. Finger, Ankit S. Tomar, Brenda Gallie, Tero T. Kivelä, Ashwin Mallipatna, Chengyue Zhang, Junyang Zhao, Matthew W. Wilson, Rachel C. Brennan, Michala Burges, Jonathan Kim, Jesse L. Berry, Rima Jubran, Vikas Khetan, Suganeswari Ganesan, Andrey Yarovoy, Vera Yarovaya, Elena Kotova, Denis Volodin, Yacoub A. Yousef, Kalle Nummi, Tatiana L. Ushakova, Olga V. Yugay, Vladimir G. Polyakov, Marco A. Ramirez-Ortiz, Elizabeth Esparza-Aguiar, Guillermo Chantada, Paula Schaiquevich, Adriana Fandino, Jason C. Yam, Winnie W. Lau, Carol P. Lam, Phillipa Sharwood, Sonia Moorthy, Quah Boon Long, Vera Adobea Essuman, Lorna A. Renner, Ekaterina Semenova, Jaume Català-Mora, Genoveva Correa-Llano, and Elisa Carreras
Subjects: Ophthalmology
Published: 2023
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20. Retinoblastoma and uveal melanoma in Jordan: incidence, demographics, and survival (2011-2020)

Author: Yacoub A. Yousef, Mona Mohammad, Ibrahim Al-Nawaiseh, Hala Mahafza, Hadeel Halalsheh, Mustafa Mehyar, Reem AlJabari, Khaleel Al-Rawashdeh, Imad Jaradat, Iyad Sultan, and Maysa Al-Hussaini
Subjects: Ophthalmology, Pediatrics, Perinatology and Child Health, Genetics (clinical)
Abstract: We present an epidemiologic analysis of retinoblastoma (RB) and uveal melanoma (UM) in Jordan to aid national strategies for improved ocular cancer surveillance and control.A retrospective cohort of all Jordanian patients with RB and UM diagnosed over 10 years (2011-2020). Outcome measures included incidence, demographics, and outcomes.Retinoblastoma (n = 124) was more common than UM (n = 82); there was no sex predilection for either group. The median age at diagnosis of RB was 15 months(Six and 28 months for bilateral and unilateral cases, respectively), and the mean age-adjusted incidence was 8.2 cases per-million-children per year for children aged five years or less(one per 15,620 newborn per year). Fifty-one(41%) had bilateral disease, and 18(15%) had familial disease. Ninety-six(55%) eyes were group D or E(78% were T3/T4), and the five-year survival rate was 96%.For UM, the median age at diagnosis was 45 years with an incidence of 1.39 new cases per year per one million population. All(100%) had nonfamilial unilateral disease. Seventy-three(89%) had the tumor in the choroid, and 48(58%) had an advanced tumor that had invaded the sclera or the orbit (T3/T4) tumor. Sixty-two(76%) were treated by I-125 radioactive plaque, with globe salvage in 59(95%); the five-year survival rate was 85%.In Jordan, RB is more common and has better survival than UM. RB in Jordan and Western countries is equal in terms of incidence, globe salvage, and survival. UM is less common, with lower age at diagnosis (that was associated with better survival) in Jordan than in Western countries.
Published: 2022

21. Global Retinoblastoma Treatment Outcomes

Author: Ekaterina Semenova, Kalle Nummi, Olga V Yugay, Carol P. S. Lam, Suganeswari Ganesan, Adriana Fandiño, Guillermo Chantada, Tero Kivelä, Elisa Carreras, Michala Burges, Phillipa Sharwood, V.G. Polyakov, Paula Schaiquevich, Vera Adobea Essuman, Quah Boon Long, Vera Yarovaya, Brenda L. Gallie, Rachel C. Brenna, Jaume Català, Paul T. Finger, Elena Kotova, Ashwin Mallipatna, Junyang Zhao, Winnie W. Y. Lau, Genoveva Correa-Llano, Tatiana L Ushakova, Ankit Singh Tomar, Jason C. S. Yam, Lorna Renner, Yacoub A. Yousef, Jonathan W. Kim, Elizabeth Esparza-Aguiar, Andrey A. Yarovoy, Vikas Khetan, Matthew W. Wilson, Sonia Moorthy, Marco A. Ramirez-Ortiz, and Chengyue Zhang
Subjects: Retinoblastoma, business.industry, Measures of national income and output, Treatment outcome, Outcome measures, Patient survival, World population, medicine.disease, Treatment failure, 3. Good health, 03 medical and health sciences, Ophthalmology, 0302 clinical medicine, 030220 oncology & carcinogenesis, 030221 ophthalmology & optometry, medicine, business, Demography, Cancer staging
Abstract: Purpose To compare metastasis-related mortality, local treatment failure, and globe salvage after retinoblastoma in countries with different national income levels. Design International, multicenter, registry-based retrospective case series. Participants Two thousand one hundred ninety patients, 18 ophthalmic oncology centers, and 13 countries on 6 continents. Methods Multicenter registry-based data were pooled from retinoblastoma patients enrolled between January 2001 and December 2013. Adequate data to allow American Joint Committee on Cancer staging, eighth edition, and analysis for the main outcome measures were available for 2085 patients. Each country was classified by national income level, as defined by the 2017 United Nations World Population Prospects, and included high-income countries (HICs), upper middle-income countries (UMICs), and lower middle-income countries (LMICs). Patient survival was estimated with the Kaplan-Meier method. Logistic and Cox proportional hazards regression models were used to determine associations between national income and treatment outcomes. Main Outcome Measures Metastasis-related mortality and local treatment failure (defined as use of secondary enucleation or external beam radiation therapy). Results Most (60%) study patients resided in UMICs and LMICs. The global median age at diagnosis was 17.0 months and higher in UMICs (20.0 months) and LMICs (20.0 months) than HICs (14.0 months; P Conclusions This international, multicenter, registry-based analysis of retinoblastoma management revealed that lower national income levels were associated with significantly higher rates of metastasis-related mortality, local treatment failure, and lower globe salvage.
Published: 2021
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22. Bilateral diffuse uveal melanocytic proliferation secondary to acute lymphoblastic leukemia: a case report

Author: Muhanad Alshathly, Mayada Abu Shanap, Yacoub A. Yousef, Mario Damiano Toro, Reham Shehada, Robert Rejdak, Katarzyna Nowomiejska, Iyad Sultan, and Mona Mohammad
Published: 2021
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23. How Telemedicine and Centralized Care Changed the Natural History of Retinoblastoma in a Developing Country

Author: Reem AlJabari, Ibrahim Qaddoumi, Nakhleh E. Abu-Yaghi, Iyad Sultan, Mustafa Mehyar, Ibrahim Al-Nawaiseh, Mona Mohammad, Matthew W. Wilson, Yacoub A. Yousef, Carlos Rodriguez-Galindo, Maysa Al-Hussaini, and Imad Jaradat
Subjects: 0303 health sciences, Telemedicine, Pediatrics, medicine.medical_specialty, Referral, business.industry, Mortality rate, Single Center, Natural history, 03 medical and health sciences, Ophthalmology, 0302 clinical medicine, Cohort, 030221 ophthalmology & optometry, Medicine, Family history, business, Developed country, 030304 developmental biology
Abstract: Objective To evaluate the efficacy of integrating telemedicine-based twinning partnership and centralized care for Retinoblastoma (RB) on survival and eye salvage. Design A cohort of 478 RB patients from 2003 to 2019 treated at tertiary referral cancer center (King Hussein Cancer Centre, KHCC). Participants 478 RB patients who were treated at KHCC after implementing a telemedicine-based program with St. Jude Children’s Research Hospital. Methods We reviewed the outcomes of RB patients who were treated at King Hussein Cancer Centre (KHCC) after implementing a telemedicine-based eye salvage program with St. Jude Children’s Research Hospital, and we compared that with outcomes for RB patients who were treated before implementing a telemedicine-based RB service at KHCC. Main Outcome Measures We analyzed patient demographics, clinical characteristics, treatments received, consultation type and duration, and long-term patient outcomes before and after implementing the twinning program. Results Over 17 years, 813 eyes from 478 children with RB were treated at KHCC, 335(70%) patients had bilateral disease, and family history of RB was positive in 6(4%) of unilateral cases, and in 66(20%) of bilateral cases. After the twinning program was established in 2003, the mortality rate decreased from 38% to 5%(P Conclusions Centralization of care at a single center in developing countries can achieve patient outcomes comparable with those of developed countries via twinning and telemedicine. This benefit can extend to a large region because two thirds of patients treated at KHCC were non-Jordanians.
Published: 2021
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24. A Multicenter, International Collaborative Study for American Joint Committee on Cancer Staging of Retinoblastoma

Author: Andrey A. Yarovoy, Jason C. S. Yam, Tero Kivelä, Brenda L. Gallie, Jonathan W. Kim, Ekaterina Semenova, Guillermo Chantada, Genoveva Correa-Llano, Adriana Fandiño, Matthew W. Wilson, Suganeswari Ganesan, Ashwin Mallipatna, Jaume Català, Sonia Moorthy, Elisa Carreras, Olga V Yugay, Ankit Singh Tomar, Junyang Zhao, Marco A. Ramirez-Ortiz, Tatiana L Ushakova, Michala Burges, Vikas Khetan, Vera Adobea Essuman, Chengyue Zhang, Winnie W. Y. Lau, V.G. Polyakov, Yacoub A. Yousef, Paula Schaiquevich, Kalle Nummi, Carol P. S. Lam, Phillipa Sharwood, Rachel C. Brenna, Paul T. Finger, Elena Kotova, Quah Boon Long, Vera Yarovaya, Lorna Renner, and Elizabeth Esparza-Aguiar
Subjects: 0303 health sciences, Chemotherapy, medicine.medical_specialty, genetic structures, Retinoblastoma, business.industry, medicine.medical_treatment, Enucleation, Cancer, medicine.disease, Intraocular Retinoblastoma, eye diseases, Treatment failure, 3. Good health, Surgery, 03 medical and health sciences, Ophthalmology, 0302 clinical medicine, Treatment success, 030221 ophthalmology & optometry, medicine, sense organs, business, 030304 developmental biology, Cancer staging
Abstract: Purpose To evaluate the ability of the American Joint Committee on Cancer (AJCC) 8th edition to predict local tumor control and globe salvage for children with retinoblastoma (RB). Design International, multicenter, registry-based retrospective case series. Participants A total of 2854 eyes of 2097 patients from 18 ophthalmic oncology centers from 13 countries over 6 continents. Methods International, multicenter, registry-based data were pooled from patients enrolled between January 2001 and December 2013. All RB eyes with adequate records to allow tumor staging by the AJCC 8th edition criteria and follow-up to ascertain treatment outcomes were included. Main Outcome Measures Globe-salvage rates were estimated by AJCC clinical (cTNMH) categories and tumor laterality. Local treatment failure was defined as use of enucleation or external beam radiation therapy (EBRT), with or without plaque brachytherapy or intra-arterial chemotherapy (IAC). Results Unilateral RB occurred in 1340 eyes (47%). Among the 2854 eyes, tumor categories were cT1 to cT4 in 696 eyes (24%), 1334 eyes (47%), 802 eyes (28%), and 22 eyes (1%), respectively. Of these, 1275 eyes (45%) were salvaged, and 1179 eyes (41%) and 400 eyes (14%) underwent primary and secondary enucleation, respectively. The 2- and 5-year Kaplan–Meier cumulative globe-salvage rates without the use of EBRT by cTNMH categories were 97% and 96% for category cT1a tumors, 94% and 88% for cT1b tumors, 68% and 60% for cT2a tumors, 66% and 57% for cT2b tumors, and 32% and 25% for cT3 tumors, respectively. Risk of local treatment failure increased with increasing cT category (P Conclusions Multicenter, international, internet-based data sharing validated the 8th edition AJCC RB staging to predict globe-salvage in a large, heterogeneous, real-world patient population with RB.
Published: 2020
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25. Rosai-Dorfman disease masquerading as Uveal Melanoma: Case report and review of literature

Author: Ibrahim Al-Nawaiseh, Khaleel Alrawashdeh, Maysa Al-Hussaini, Yacoub A. Yousef, Rashed Mustafa Nazzal, and Ghadeer Abdeen
Subjects: Uveal Neoplasms, Pathology, medicine.medical_specialty, Adolescent, genetic structures, Ciliary body, lcsh:RC254-282, Serous Retinal Detachment, Diagnosis, Differential, Biopsy, medicine, Humans, Melanoma, Rosai–Dorfman disease, medicine.diagnostic_test, business.industry, lcsh:RC633-647.5, Ciliary body melanoma, Hematology, General Medicine, lcsh:Diseases of the blood and blood-forming organs, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, eye diseases, medicine.anatomical_structure, Oncology, Female, Choroid, sense organs, Histiocytosis, Sinus, business, Rare disease, Rosai-Dorfman
Abstract: Objective/Background Intra ocular Rosai-Dorfman disease (RDD) is an extremely rare disease. We are reporting the first case of RDD presenting as ciliary body mass mimicking ciliary body melanoma, and we are reviewing the English literature reporting on cases of RDD presented with intraocular disease. Methods An 18-year-old lady presented with loss of vision in the right eye, and was found to have intraocular mass lesion. She was diagnosed clinically and radiologically as a case of ciliary body melanoma associated with total retinal detachment. Results Histopathological sections and stains proved to be intraocular RDD. Review of the literature revealed three cases of intraocular RDD; two of them had choroid thickening associated with serous retinal detachment, and one presented with intraocular mass mimicking choroid melanoma. Two of the three cases were enucleated. Our case is the first case in English literature of intraocular ciliary body RDD, mimicking ciliary body melanoma. Conclusion RDD can present as an intraocular mass that mimics ciliary body melanoma. This case emphasizes the importance of diagnostic biopsy before considering the final therapy in unclear cases, mainly when associated with unusual systemic features like lymphadenopathy.
Published: 2020

26. A Multicenter, International Collaborative Study for American Joint Committee on Cancer Staging of Retinoblastoma

Author: Kalle Nummi, Carol P. S. Lam, Phillipa Sharwood, Tero Kivelä, Brenda L. Gallie, Adriana Fandiño, Quah Boon Long, Vera Yarovaya, Guillermo Chantada, Sonia Moorthy, Jason C. S. Yam, Tatiana L Ushakova, Jaume Català, Matthew W. Wilson, Marco A. Ramirez-Ortiz, Winnie W. Y. Lau, Lorna Renner, Junyang Zhao, Ashwin Mallipatna, Chengyue Zhang, Ankit Singh Tomar, Vikas Khetan, V.G. Polyakov, Vera Adobea Essuman, Elizabeth Esparza-Aguiar, Suganeswari Ganesan, Jonathan W. Kim, Olga V Yugay, Genoveva Correa-Llano, Andrey A. Yarovoy, Paula Schaiquevich, Paul T. Finger, Elena Kotova, and Yacoub A. Yousef
Subjects: 0303 health sciences, medicine.medical_specialty, Trilateral retinoblastoma, business.industry, Mortality rate, Enucleation, Cancer, medicine.disease, Confidence interval, 3. Good health, Metastasis, 03 medical and health sciences, Ophthalmology, 0302 clinical medicine, Internal medicine, 030221 ophthalmology & optometry, Medicine, business, Pathological, 030304 developmental biology, Cancer staging
Abstract: Purpose To evaluate the ability of the 8th edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual to estimate metastatic and mortality rates for children with retinoblastoma (RB). Design International, multicenter, registry-based retrospective case series. Participants A total of 2190 patients from 18 ophthalmic oncology centers from 13 countries over 6 continents. Methods Patient-specific data fields for RB were designed and selected by subcommittee. All patients with RB with adequate records to allow tumor staging by the AJCC criteria and follow-up for metastatic disease were studied. Main Outcome Measures Metastasis-related 5- and 10-year survival data after initial tumor staging were estimated with the Kaplan–Meier method depending on AJCC clinical (cTNM) and pathological (pTNM) tumor, node, metastasis category and age, tumor laterality, and presence of heritable trait. Results Of 2190 patients, the records of 2085 patients (95.2%) with 2905 eyes were complete. The median age at diagnosis was 17.0 months. A total of 1260 patients (65.4%) had unilateral RB. Among the 2085 patients, tumor categories were cT1a in 55 (2.6%), cT1b in 168 (8.1%), cT2a in 197 (9.4%), cT2b in 812 (38.9%), cT3 in 835 (40.0%), and cT4 in 18 (0.9%). Of these, 1397 eyes in 1353 patients (48.1%) were treated with enucleation. A total of 109 patients (5.2%) developed metastases and died. The median time (n = 92) from diagnosis to metastasis was 9.50 months. The 5-year Kaplan–Meier cumulative survival estimates by clinical tumor categories were 100% for category cT1a, 98% (95% confidence interval [CI], 97–99) for cT1b and cT2a, 96% (95% CI, 95–97) for cT2b, 89% (95% CI, 88–90) for cT3 tumors, and 45% (95% CI, 31–59) for cT4 tumors. Risk of metastasis increased with increasing cT (and pT) category (P Conclusions Multicenter, international, internet-based data sharing facilitated analysis of the 8th edition AJCC RB Staging System for metastasis-related mortality and offered a proof of concept yielding quantitative, predictive estimates per category in a large, real-life, heterogeneous patient population with RB.
Published: 2020
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27. Prognostic Factors for Eye Globe Salvage by External Beam Radiation Therapy for Resistant Intraocular Retinoblastoma

Author: Mustafa Mehyar, Imad Jaradat, Raed Shatnawi, Mona Mohammad, Yacoub A. Yousef, and Ibrahim Al-Nawaiseh
Subjects: medicine.medical_specialty, Radiation retinopathy, genetic structures, medicine.medical_treatment, Enucleation, Intraocular Retinoblastoma, retinoblastoma, Metastasis, lcsh:Ophthalmology, medicine, business.industry, Retinoblastoma, Retinal detachment, medicine.disease, eye diseases, Radiation therapy, Ophthalmology, lcsh:RE1-994, Vitreous hemorrhage, vitreous seeds, Original Article, Radiology, sense organs, business, stage migration
Abstract: PURPOSE: To analyse the prognostic factors for eye salvage for eyes with intra-ocular retinoblastoma (RB) that is resistant to systemic chemotherapy and focal therapy by external beam radiation therapy (EBRT). METHODS: A retrospective analysis of 28 eyes with intra-ocular RB that was resistant for systemic chemotherapy and focal consolidation therapy and received EBRT. Outcome measures included tumor stage at diagnosis, stage migration, type of tumor seeds, treatment modalities, eye globe salvage, metastasis, and survival. RESULTS: Most of the patients (83%) had bilateral RB, and 42% were females. All eyes were treated initially by combination of systemic chemotherapy and focal consolidation therapy. The dose of EBRT was 45 Gy. The mean follow-up was 6.5 years, and the overall eye globe salvage rate post EBRT was 46%: 67% (2/3) for group B, 71% (5/7) for group C, and 33% (6/18) for group D. Patient's gender, tumor site, laterality, and tumor stage at diagnosis were not significant prognostic factors (p> 0.05) for final outcome. The significant poor prognostic factors were tumor stage migration during systemic chemotherapy (p= 0.03) and presence of vitreous seeds at time of EBRT (p=0.001). Post EBRT complication rate was 68% (19/28) including; retinal detachment (3), vitreous hemorrhage (4), neovascular glaucoma (1), cataract (16), radiation retinopathy (2), and second malignancy (2). CONCLUSION: EBRT is an alternative for enucleation when RB is resistant to combined chemoreduction/focal consolidation therapy in absence in vitreous seeds. The known risks for EBRT are not justified for patients with unilateral RB and for those who have functional vision in the other eye.
Published: 2020

28. Impact of RB1 gene mutation type in retinoblastoma patients on clinical presentation and management outcome

Author: Ibrahim Al-Nawaiseh, Imad Jaradat, Mohammad Mosallam, Reem AlJabari, Abdelghani Tbakhi, Ala Saab, Iyad Sultan, Maysa Al-Hussaini, Mustafa Mehyar, Mona Mohammad, Yacoub A. Yousef, and Rasha Deebajah
Subjects: Oncology, Male, medicine.medical_specialty, Adolescent, Germline, Ubiquitin-Protein Ligases, Nonsense mutation, medicine.disease_cause, Malignancy, lcsh:RC254-282, Frameshift mutation, 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, Internal medicine, medicine, Humans, Child, Germ-Line Mutation, Sanger sequencing, RB1 gene, Mutation, Retinoblastoma, business.industry, lcsh:RC633-647.5, Eye Neoplasms, Hematology, General Medicine, lcsh:Diseases of the blood and blood-forming organs, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Stop codon, eye diseases, Retinoblastoma Binding Proteins, 030220 oncology & carcinogenesis, Child, Preschool, symbols, Female, business, 030215 immunology
Abstract: Objective/background Retinoblastoma (RB), the most common intraocular malignancy in children, is caused by biallelic inactivation of the human retinoblastoma susceptibility gene (RB1). We are evaluating the impact of the type of RB1 gene mutation on clinical presentation and management outcome. Methods A retrospective case series of 50 patients with RB. Main outcomes were clinical and pathologic features and types of RB1 gene mutations detected using quantitative multiplex polymerase chain reaction (PCR), allele-specific PCR, next-generation sequencing analysis, and Sanger sequencing. Results Twenty (40%) patients had unilateral RB and 30 (60%) had bilateral RB. Overall, 36 (72%) patients had germline disease, 17 (47%) of whom inherited the disease. Of these 17 inherited cases, paternal origin of the RB1 mutation was seen in 15 (88%). The overall eye salvage rate was 74% (n = 49/66; 100% for Groups A + B + C, and 79% for Group D eyes). The most frequent type of mutation was a nonsense mutation generating a stop codon (15/36, 42%). Other mutations that result in a premature stop codon due to deletions or insertions with donor splice site or receptor splice site mutations were detected in 7/36 (19%), 10/36 (28%), and 2/26 (6%) patients, respectively. The remaining two (6%) patients had frameshift mutation. Patients with deletion, acceptor splice site, and frameshift mutations presented with more advanced ICRB (International Classification of Retinoblastoma) stage (75% diagnosed with Group D or E), even though there was no significant difference in eye salvage rate or tumor invasiveness between patients with different types of mutations. Conclusion Despite the heterogeneous nature of RB1 gene mutations, tumor stage remains the most important predictive factor for clinical presentation and outcome. Furthermore, acceptor splice site and frameshift mutations are associated with more advanced tumor stage at diagnosis.
Published: 2020

29. A Proposal for Future Modifications on Clinical TNM Staging System of Retinoblastoma Based on the American Joint Committee on Cancer Staging Manual, 7 th and 8 th Editions

Author: Yacoub A. Yousef, Ibrahim Qaddoumi, Ibrahim Al-Nawaiseh, Mona Mohammad, Dalia AlRimawi, Mario Damiano Toro, Sandrine Zweifel, Robert Rejdak, Rashed Nazzal, Mustafa Mehyar, Imad Jaradat, Iyad Sultan, Maysa Al-Hussaini, Yousef, Ya, Qaddoumi, I, Al-Nawaiseh, I, Mohammad, M, Alrimawi, D, Toro, Md, Zweifel, S, Rejdak, R, Nazzal, R, Mehyar, M, Jaradat, I, Sultan, I, and Al-Hussaini, M
Subjects: Oncology
Published: 2022

30. Imaging of Uveal Melanoma—Current Standard and Methods in Development

Author: Małgorzata Solnik, Natalia Paduszyńska, Anna M. Czarnecka, Kamil J. Synoradzki, Yacoub A. Yousef, Tomasz Chorągiewicz, Robert Rejdak, Mario Damiano Toro, Sandrine Zweifel, Katarzyna Dyndor, Michał Fiedorowicz, Solnik, M., Paduszynska, N., Czarnecka, A. M., Synoradzki, K. J., Yousef, Y. A., Choragiewicz, T., Rejdak, R., Toro, M. D., Zweifel, S., Dyndor, K., and Fiedorowicz, M.
Subjects: Cancer Research, diagnosi, PET, Oncology, OCT, SPECT, imaging, ultrasonography, uveal melanoma, CT, MRI
Abstract: Uveal melanoma is the most common primary intraocular malignancy in adults, characterized by an insidious onset and poor prognosis strongly associated with tumor size and the presence of distant metastases, most commonly in the liver. Contrary to most tumor identification, a biopsy followed by a pathological exam is used only in certain cases. Therefore, an early and noninvasive diagnosis is essential to enhance patients’ chances for early treatment. We reviewed imaging modalities currently used in the diagnostics of uveal melanoma, including fundus imaging, ultrasonography (US), optical coherence tomography (OCT), single-photon emission computed tomography (SPECT), fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA), fundus autofluorescence (FAF), as well as positron emission tomography/computed tomography (PET/CT) or magnetic resonance imaging (MRI). The principle of imaging techniques is briefly explained, along with their role in the diagnostic process and a summary of their advantages and limitations. Further, the experimental data and the advancements in imaging modalities are explained. We describe UM imaging innovations, show their current usage and development, and explain the possibilities of utilizing such modalities to diagnose uveal melanoma in the future.
Published: 2022

31. A comparison of high risk pathological features between primary and secondary enucleation for retinoblastoma

Author: Mona Mohammad, Reham Shehada, Ibrahim Al-Nawaiseh, Mustafa Mehyar, Maysa AlHussaini, Imad Jaradat, Iyad Sultan, Hadeel Halalsheh, Jakub Khzouz, and Yacoub A Yousef
Subjects: Ophthalmology, General Medicine
Abstract: Aim To compare the risk and pattern of High-Risk Pathologic Features (HRPF) in retinoblastoma between primary and secondary enucleation. Methods A retrospective analysis of 121 eyes from 118 patients who underwent enucleation at the King Hussein Cancer Center (KHCC) Amman, Jordan, between November 2009 and January 2020. Demographic information, tumor stage, time from diagnosis–to-enucleation, results of pathology, metastasis, and mortality were retrieved. Results Patients in the secondary group (49/121 eyes, 40%) were considerably younger at diagnosis (p = 0.0014), had bilateral disease (p = 0.0001), and had less-progressed disease at presentation (p = 0.016) compared to the primary enucleation. Primarily enucleated eyes were more-likely to have massive choroidal invasion (p = 0.0315) and post-laminar optic nerve invasion (p = 0.027), in spite of the finding that the overall prevalence of HRPF was similar between the two groups (35.5 percent vs. 37.5 percent; p = 0.585). The likelihood of anterior chamber invasion, was considerably higher in secondary enucleated eyes (p = 0.013). We evaluated primary and secondary enucleation for each subgroup (D and E) of the International Intraocular Retinoblastoma Classification (IIRC) and found the prevalence of HRPF was comparable (p = 0.58, 1.0, respectively). The difference in time between diagnosis-to-enucleation in secondary enucleation did not predict HRPF (p = 0.50). There was no discernible difference between primary and secondary enucleated eyes in terms of metastasis or survival (p = 0.156 and 0.44, respectively). Conclusion Systemic chemotherapy has the ability to reduce the extent of tumor expansion that has been pathologically identified. Primary and secondary enucleated eyes are comparable in low metastatic risk only when strict examination and management guidelines are followed.
Published: 2023
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32. New Perspectives in Imaging of Uveal Melanoma

Author: Katarzyna Dyndor, Natalia Paduszynska, Michal Fiedorowicz, Mario Damiano Toro, Robert Rejdak, Malgorzata Solnik, Kamil Synoradzki, Yacoub A. Yousef, Anna M. Czarnecka, and Tomasz Choragiewicz
Subjects: ophthalmology, medicine.medical_specialty, genetic structures, business.industry, Melanoma, medicine, sense organs, Radiology, Ultrasonography, business, medicine.disease, eye diseases
Abstract: Uveal melanoma is the most common primary intraocular malignancy in adults characterized by insidious onset and poor prognosis strongly associated with tumor size and the presence of distant metastases, most commonly in the liver. Contrary to most tumor identification, biopsy followed by pathological exam is not recommended in ophthalmic oncology. Therefore, early and non-invasive diagnosis is essential to enhance patients’ chances for early treatment possibilities. We reviewed imaging modalities currently used in the diagnosis of uveal melanoma, i.e., fundus imaging, ultrasonography (US), optical coherence tomography (OCT), single-photon emission computed tomography (SPECT), positron emission tomography/computed tomography (PET/CT), magnetic resonance imaging (MRI), fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA), fundus autofluorescence (FAF). The principle of imaging techniques was briefly explained, along with their role in the diagnostic process and a summary of their advantages and limitations. Further, the experimental data and the advancements in imaging modalities were searched. We described their innovations, showed current usage and research, and explained the possibilities of utilizing them to diagnose uveal melanoma and their potential application in personalized medicine such as theranostics.
Published: 2021
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33. New Therapeutic Perspectives in the Treatment of Uveal Melanoma: A Systematic Review

Author: Filippo Drago, Luciano Tracia, Teresio Avitabile, Yacoub A. Yousef, Katarzyna Nowomiejska, Giovanni Luca Romano, Claudio Bucolo, Sandrine Zweifel, Robert Rejdak, Lucia Gozzo, Rashed Mustafa Nazzal, Marco Cicciù, Mario Damiano Toro, Toro, mario damiano, Gozzo, Lucia, Tracia, Luciano, Cicciù, Marco, Drago, Filippo, Bucolo, Claudio, Avitabile, Teresio, Rejdak, Robert, Nowomiejska, Katarzyna, Zweifel, Sandrine, Yousef, Yacoub A., Nazzal, Rashed, Luca Romano, Giovanni, and University of Zurich
Subjects: 10018 Ophthalmology Clinic, medicine.medical_specialty, QH301-705.5, medicine.medical_treatment, Medicine (miscellaneous), 610 Medicine & health, Disease, General Biochemistry, Genetics and Molecular Biology, Local treatment, Pharmacological treatment, Systemic treatment, Treatment strategies, Uveal melanoma, pharmacological treatment, local treatment, 1300 General Biochemistry, Genetics and Molecular Biology, treatment strategies, medicine, Biology (General), Adverse effect, Intensive care medicine, business.industry, Melanoma, Cancer, 2701 Medicine (miscellaneous), systemic treatment, medicine.disease, Radiation therapy, Clinical trial, medicine.anatomical_structure, Choroid, Systematic Review, uveal melanoma, business, Rare disease
Abstract: Uveal melanoma (UM) is a rare disease, but the most common primary intraocular cancer, mostly localized in the choroid. Currently, the first-line treatment options for UM are radiation therapy, resection, and enucleation. However, although these treatments could potentially be curative, half of all patients will develop metastatic disease, whose prognosis is still poor. Indeed, effective therapeutic options for patients with advanced or metastatic disease are still lacking. Recently, the development of new treatment modalities with a lower incidence of adverse events, a better disease control rate, and new therapeutic approaches, have merged as new potential and promising therapeutic strategies. Additionally, several clinical trials are ongoing to find new therapeutic options, mainly for those with metastatic disease. Many interventions are still in the preliminary phases of clinical development, being investigated in phase I trial or phase I/II. The success of these trials could be crucial for changing the prognosis of patients with advanced/metastatic UM. In this systematic review, we analyzed all emerging and available literature on the new perspectives in the treatment of UM and patient outcomes; furthermore, their current limitations and more common adverse events are summarized.
Published: 2021

34. Retinoblastoma and prune belly syndrome: the first described association in literature

Author: Agata Pietras-Baczewska, Mustafa Mehyar, Rafat Turki, Robert Rejdak, Rashed Mustafa Nazzal, Ibrahim Al-Nawaiseh, Ewa Jasińska, and Yacoub A. Yousef
Subjects: EAGLE-BARRETT SYNDROME, Pediatrics, medicine.medical_specialty, business.industry, Retinoblastoma, Leukocoria, medicine.disease, eye diseases, Left eye, Prune belly syndrome, medicine, Intraocular tumor, Congenital disease, medicine.symptom, business
Abstract: Background: Retinoblastoma is the most common primary intraocular tumor in children. Prune belly syndrome is a rare congenital disease affecting newborns. The combination of the two diseases has never been reported before. In this article, we present a case of a male infant diagnosed with prune belly syndrome (PBS) at birth. Case report: Patient underwent many surgeries to manage the resulting consequences of PBS. At the age of 7 months, he presented with left eye leukocoria. He was examined and diagnosed with retinoblastoma. The eye was enucleated, and the diagnosis was confirmed histopathologically. This is the first case to be described in the literature of such an association to the best of our knowledge. Key words: prune belly syndrome; retinoblastoma; Eagle-Barrett syndrome
Published: 2020
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35. Retinoma — the first identified case in Jordan

Author: Robert Rejdak, Katarzyna Nowomiejska, Rashed Mustafa Nazzal, and Yacoub A. Yousef
Subjects: medicine.medical_specialty, genetic structures, medicine.diagnostic_test, business.industry, Retinocytoma, Fundus photography, Asymptomatic, eye diseases, Vitreous cavity, medicine, sense organs, Radiology, Differential diagnosis, medicine.symptom, Intraocular tumor, Young female, business, Astrocytic hamartoma
Abstract: Retinoma (or retinocytoma) is a rare benign intraocular tumor with characteristic features and can be diagnosed clinically. In this article, we present a case report and a review of literature about retinoma. The case is about an incidentally diagnosed retinoma in an asymptomatic young female who presented for vision checkup and was found to have an intraocular translucent-grey, elevated mass extending into the vitreous cavity from the retina with the characteristic features of retinoma. The main differential diagnosis included retinoblastoma and astrocytic hamartoma. The mass showed no growth over a period of 6 months of follow up with colored fundus photography and ultrasound. This case is, to the best of our knowledge, the first case of retinoma diagnosed in Jordan.
Published: 2019
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36. Characteristics, management, and outcome of ocular medulloepithelioma: systematic review of literature and case report

Author: Hanood Abu-Rass, Iyad Sultan, Yacoub A. Yousef, Mays AlJboor, Hussam Haddad, Katarzyna Nowomiejska, Rashed Mustafa Nazzal, and Shatha Hajja
Subjects: medicine.medical_specialty, Retinoblastoma, business.industry, medicine.medical_treatment, Enucleation, medicine.disease, Malignancy, eye diseases, Metastasis, Radiation therapy, Pleomorphism (cytology), medicine, Histopathology, Radiology, Medulloepithelioma, business
Abstract: Background: Ocular medulloepithelioma (OM) is a rare ocular malignancy. This is a report of a rare case of medulloepithelioma that was misdiagnosed as retinoblastoma. Material and methods: A case report and review of published, peer-reviewed, English language literature reporting on ocular medulloepithelioma. Results: A seven-year-old girl presented with a white mass in the anterior chamber of her left eye. The initial diagnosis was retinoblastoma with anterior chamber invasion, and therefore it was enucleated. Microscopy showed a cellular tumour composed of malignant primitive cells forming sheets, rosettes, and tubular structures. Based on the presence of prominent pleomorphism the tumour was diagnosed as malignant teratoid medulloepithelioma. At last date of follow-up three years after enucleation, the patient was alive without metastasis. A systematic review of literature, analysed 177 cases of OM. The tumour was localised in the ciliary body in 134 (92%) cases, and 26 (23%) cases had extraocular extension. Primary management was enucleation in 84 (55%) cases, tumour resection in 32 (21%) cases, and radiation therapy in 20 (13%) cases. Histopathology disclosed benign features in 36 (22%) eyes, malignant features in 124 (78%) eyes, teratoid features in 72 (59%), and non-teratoid features in 51 (41%) eyes. At a mean follow-up of five years, 14 (8%) patients had metastasis, and six (6%) patients were dead. Conclusions: Ocular medulloepithelioma most commonly affects children. The most common type is the malignant teratoid type, but it has a favourable prognosis, and distant metastasis and mortality are relatively rare, at 8% and 6%, respectively.
Published: 2019
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37. Retinoblastoma awareness among first contact physicians in Jordan

Author: Ibrahim Al-Nawaiseh, Sana Muhsen, Reem AlJabari, Tamara Alnawaiseh, and Yacoub A. Yousef
Subjects: Adult, Male, 0301 basic medicine, First contact, Health Knowledge, Attitudes, Practice, Pediatrics, medicine.medical_specialty, Students, Medical, genetic structures, Retinal Neoplasms, Leukocoria, 030105 genetics & heredity, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Surveys and Questionnaires, Humans, Medicine, Pediatricians, Child, Genetics (clinical), Jordan, Ophthalmologists, business.industry, Retinoblastoma, medicine.disease, eye diseases, Ophthalmology, Cross-Sectional Studies, Pediatrics, Perinatology and Child Health, 030221 ophthalmology & optometry, Female, Clinical Competence, medicine.symptom, business, Education, Medical, Undergraduate
Abstract: Background: Early diagnosis and timely management of Retinoblastoma (RB) patients are essential to improve eye salvage and survival rates. The objective of this study is to evaluate the lev...
Published: 2019
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38. A Proposal for Future Modifications on Clinical TNM Staging System of Retinoblastoma Based on the American Joint Committee on Cancer Staging Manual, 7

Author: Yacoub A, Yousef, Ibrahim, Qaddoumi, Ibrahim, Al-Nawaiseh, Mona, Mohammad, Dalia, AlRimawi, Mario Damiano, Toro, Sandrine, Zweifel, Robert, Rejdak, Rashed, Nazzal, Mustafa, Mehyar, Imad, Jaradat, Iyad, Sultan, and Maysa, Al-Hussaini
Published: 2021

39. Safety and Efficacy of Intravitreal Chemotherapy (Melphalan) to Treat Vitreous Seeds in Retinoblastoma

Author: Mona Mohammad, Yacoub A. Yousef, Mutasem Elfalah, Mays Al Jboor, Mustafa Mehyar, Rashed Mustafa Nazzal, Robert Rejdak, Magdalena Rejdak, Qusai H Alzureikat, Mario Damiano Toro, Maysa Al-Hussaini, Iyad Sultan, Ibrahim Al-Nawaiseh, Yousef, Ya, Al Jboor, M, Mohammad, M, Mehyar, M, Toro, Md, Nazzal, R, Alzureikat, Qh, Rejdak, M, Elfalah, M, Sultan, I, Rejdak, R, Al-Hussaini, M, and Al-Nawaiseh, I
Subjects: Melphalan, medicine.medical_specialty, genetic structures, medicine.medical_treatment, Enucleation, RM1-950, chemotherapy, retinoblastoma, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Atrophy, Refractory, Cataracts, Ophthalmology, medicine, Pharmacology (medical), Original Research, ocular toxicity, Pharmacology, Chemotherapy, business.industry, food and beverages, Retinal, medicine.disease, eye diseases, melphalan, chemistry, Toxicity, 030221 ophthalmology & optometry, vitreous seeds, Therapeutics. Pharmacology, sense organs, business, 030217 neurology & neurosurgery, medicine.drug
Abstract: Background: Active vitreous seeds in eyes with retinoblastoma (Rb) adversely affects the treatment outcome. This study aimed to investigate the safety and efficacy of intravitreal melphalan chemotherapy (IViC) as a treatment for recurrent and refractory vitreous seeds in patients with Rb.Methods: We used a retrospective non-comparative study of patients with intraocular Rb who had vitreous seeds and were treated by IViC (20–30 μg of melphalan) using the safety-enhanced anti-reflux technique. Tumor response, ocular toxicity, demographics, clinical features, and survival were analyzed.Results: In total, 27 eyes were treated with 108 injections for recurrent (16 eyes) or refractory (11 eyes) vitreous seeds after failed systemic chemotherapy. A total of 15 (56%) were males, and 20 (74%) had bilateral disease. At diagnosis, the majority (n = 21) of the injected eyes were group D, and n = 6 were group C. Vitreous seeds showed complete regression in 21 (78%) eyes; 100% (n = 10) for eyes with focal seeds; 65% (n = 11/17 eyes) for eyes with diffuse seeds (p = 0.04); 7 (64%) eyes with refractory seeds; and 14 (87%) eyes with recurrent seeds showed complete response (p = 0.37). In total, 16 (59%) eyes developed side effects: retinal toxicity (48%), pupillary synechiae (15%), cataracts (30%), iris atrophy (7%), and retinal and optic atrophy (4%). Only one child was lost to follow-up whose family refused enucleation and none developed orbital tumor recurrence or distant metastasis.Conclusion: IViC with melphalan is effective (more for focal than diffuse seeding) and a relatively safe treatment modality for Rb that can improve the outcomes of eye salvage procedures. However, unexpected toxicity can occur even with the standard dose of 20–30 μg.
Published: 2021

40. Delayed Intravitreal Anti-VEGF Therapy for Patients During the COVID-19 Lockdown: An Ethical Endeavor

Author: Robert Rejdak, Yacoub A. Yousef, Mutasem Elfalah, Mo'ath AlShawabkeh, Sandrine Zweifel, Jehad Meqbil, Saif Aldeen AlRyalat, Amal Alwreikat, Muawyah D Al Bdour, Mario Damiano Toro, Maysa Al-Hussaini, Mohammed Abu-Ameerh, Osama H. Ababneh, Rashed Mustafa Nazzal, Almutez M. Gharaibeh, Zuhair Sharif, University of Zurich, Elfalah, Mutasem, Toro, Mario Damiano, Elfalah, M., Alryalat, S. A., Toro, M. D., Rejdak, R., Zweifel, S., Nazzal, R., Abu-Ameerh, M., Ababneh, O., Gharaibeh, A., Sharif, Z., Meqbil, J., Alshawabkeh, M., Alwreikat, A., Bdour, M. A., Al-Hussaini, M., and Yousef, Y. A.
Subjects: 10018 Ophthalmology Clinic, medicine.medical_specialty, Visual acuity, Distance visual acuity, Central retinal vein thrombosis, Coronavirus disease 2019 (COVID-19), genetic structures, macular edema, 610 Medicine & health, 03 medical and health sciences, 0302 clinical medicine, covid-19 lockdown, Ophthalmology, medicine, Ethic, Macular edema, Original Research, Anti vegf, business.industry, covid-19 pandemic, intravitreal injection, Retrospective cohort study, Clinical Ophthalmology, Macular degeneration, RE1-994, medicine.disease, 2731 Ophthalmology, ethics, eye diseases, 030221 ophthalmology & optometry, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: Mutasem Elfalah,1 Saif Aldeen AlRyalat,1 Mario Damiano Toro,2– 4 Robert Rejdak,4 Sandrine Zweifel,3 Rashed Nazzal,5 Mohammed Abu-Ameerh,1 Osama Ababneh,1 Almutez Gharaibeh,1 Zuhair Sharif,1 Jehad Meqbil,1 Mo’ath AlShawabkeh,1 Amal Alwreikat,6 Muawyah Al Bdour,1 Maysa Al-Hussaini,7 Yacoub A Yousef8 1Department of Special Surgery, Faculty of Medicine, The University of Jordan, Amman, Jordan; 2Faculty of Medical Sciences, Collegium Medicum, Cardinal Stefan WyszyÅski University, Warsaw, Poland; 3Department of Ophthalmology, University Hospital of Zürich, Zürich, Switzerland; 4Department of General Ophthalmology, Medical University of Lublin, Lublin, Poland; 5Shami Eye Center, Amman, Jordan; 6Department of Ophthalmology, Royal Medical Services, Amman, Jordan; 7Department of Pathology and Laboratory Medicine, King Hussein Cancer Center, Amman, Jordan; 8Department of Surgery (Ophthalmology), King Hussein Cancer Center, Amman, JordanCorrespondence: Mutasem ElfalahDepartment of Special Surgery, Faculty of Medicine, The University of Jordan, Queen Rania St, Amman, 11941, JordanTel +96265355000Email mutasemrabie@hotmail.comMario Damiano ToroDepartment of Ophthalmology, University Hospital of Zürich, Raemistrasse 100, Zürich, 8091, SwitzerlandTel +39 3495158220Email toro.mario@email.itPurpose: To assess the impact of Jordanian’s Corona Virus Disease (COVID-19) lockdown on visual acuity and macular thickness in patients with macular edema receiving intravitreal injections, and to assess the ethical endeavor of lockdown among serious sight threatening conditions.Patients and Methods: This retrospective observational study included patients planned for intravitreal injections who did not complete the planned course before the lockdown (ie, before 20th of March 2020). Data included demographics, indication for the intravitreal injection, corrected distance visual acuity (CDVA), and central macular thickness on Optical Coherence Tomography (OCT) before and after the lockdown.Results: One-hundred and sixty-six eyes of 125 patients were studied, 68 (54.4%) patients were males, and the mean (± standard deviation, SD) age was 64.79 (± 9.41) years. Mean (±SD) duration of delay in the planned injection was 60.97 (± 24.35) days. The change in visual acuity was statistically significant for patients with diabetic macular edema (p= 0.045 improvement), patients with central retinal vein thrombosis (CRVO) (p= 0.05 deterioration), and patients with age-related macular degeneration (AMD) (p= 0.005 deterioration). Of interest, delay of more than 2 months and the previous need for 3 or more injections were significant poor prognostic factors for visual outcome for patients with diabetic macular edema (p=0.027 and 0.045).Conclusion: The impact of delay in the scheduled intravitreal injections resulted in variable outcomes depending on the indication. Triaging the urgency of patients should be based on the indication to support the equity principle of bioethics, where those in need are prioritized against others, depending on potential adverse outcome.Keywords: COVID-19 lockdown, COVID-19 pandemic, ethics, intravitreal injection, macular edema
Published: 2021
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41. POLITENESS MAXIMS IN SAAD AL-HARIRI’S AND FRANÇOIS HOLLANDE’S SPEECHES ON REFUGEES.

Author: Abdulsada, Mohammed Nasser and Yacoub, Balsam Yousef
Published: 2022
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42. Global Retinoblastoma Treatment Outcomes: Association with National Income Level

Author: Ankit Singh, Tomar, Paul T, Finger, Brenda, Gallie, Tero T, Kivelä, Ashwin, Mallipatna, Chengyue, Zhang, Junyang, Zhao, Matthew W, Wilson, Rachel C, Brenna, Michala, Burges, Jonathan, Kim, Vikas, Khetan, Suganeswari, Ganesan, Andrey, Yarovoy, Vera, Yarovaya, Elena, Kotova, Yacoub A, Yousef, Kalle, Nummi, Tatiana L, Ushakova, Olga V, Yugay, Vladimir G, Polyakov, Marco A, Ramirez-Ortiz, Elizabeth, Esparza-Aguiar, Guillermo, Chantada, Paula, Schaiquevich, Adriana, Fandino, Jason C, Yam, Winnie W, Lau, Carol P, Lam, Phillipa, Sharwood, Sonia, Moorthy, Quah Boon, Long, Vera Adobea, Essuman, Lorna A, Renner, Ekaterina, Semenova, Jaume, Català, Genoveva, Correa-Llano, and Elisa, Carreras
Subjects: Male, Salvage Therapy, Databases, Factual, Retinal Neoplasms, Brachytherapy, Retinoblastoma, Infant, Global Health, Medical Oncology, Eye Enucleation, Treatment Outcome, Child, Preschool, Income, Humans, Female, Registries, Treatment Failure, Retrospective Studies
Abstract: To compare metastasis-related mortality, local treatment failure, and globe salvage after retinoblastoma in countries with different national income levels.International, multicenter, registry-based retrospective case series.Two thousand one hundred ninety patients, 18 ophthalmic oncology centers, and 13 countries on 6 continents.Multicenter registry-based data were pooled from retinoblastoma patients enrolled between January 2001 and December 2013. Adequate data to allow American Joint Committee on Cancer staging, eighth edition, and analysis for the main outcome measures were available for 2085 patients. Each country was classified by national income level, as defined by the 2017 United Nations World Population Prospects, and included high-income countries (HICs), upper middle-income countries (UMICs), and lower middle-income countries (LMICs). Patient survival was estimated with the Kaplan-Meier method. Logistic and Cox proportional hazards regression models were used to determine associations between national income and treatment outcomes.Metastasis-related mortality and local treatment failure (defined as use of secondary enucleation or external beam radiation therapy).Most (60%) study patients resided in UMICs and LMICs. The global median age at diagnosis was 17.0 months and higher in UMICs (20.0 months) and LMICs (20.0 months) than HICs (14.0 months; P0.001). Patients in UMICs and LMICs reported higher rates of disease-specific metastasis-related mortality and local treatment failure. As compared with HICs, metastasis-related mortality was 10.3-fold higher for UMICs and 9.3-fold higher for LMICs, and the risk for local treatment failure was 2.2-fold and 1.6-fold higher, respectively (all P0.001).This international, multicenter, registry-based analysis of retinoblastoma management revealed that lower national income levels were associated with significantly higher rates of metastasis-related mortality, local treatment failure, and lower globe salvage.
Published: 2020

43. Programmed screening for retinoblastoma enhances early diagnosis and improves management outcome for high-risk children

Author: Mays AlJboor, Hadeel Halalsheh, Maysa Al-Hussaini, Iyad Sultan, Ibrahim Al-Nawaiseh, Munir Shawagfeh, Abdelrahman Alkhoms, Maha Lahlouh, Imad Jaradat, Mona Mohammad, Yacoub A. Yousef, Rasha Deebajah, Reem AlJabari, and Mustafa Mehyar
Subjects: Oncology, Male, medicine.medical_specialty, Retinal Neoplasms, Visual Acuity, Outcome (game theory), Internal medicine, Medicine, Humans, Mass Screening, Rb1 gene, Genetics (clinical), Genetic testing, Retrospective Studies, medicine.diagnostic_test, business.industry, Retinoblastoma, Disease Management, Infant, medicine.disease, humanities, body regions, Ophthalmology, Early Diagnosis, Child, Preschool, Pediatrics, Perinatology and Child Health, Female, business
Abstract: To study the impact of a Retinoblastoma (Rb) screening program in the absence of genetic testing on the management and outcome of high-risk children.This is a retrospective, clinical case series of 76 children from families involved in a Rb screening program as they had higher than normal risk as calculated by the conventional ways without genetic testing. Data included calculated risk, method of diagnosis, demographics, tumor features, treatment modalities, and management outcome.Out of the 76 children screened, 46 children were diagnosed with Rb (12 by screening and 34 had signs of Rb), the other 30 were free of disease. Patients diagnosed by screening were younger (mean; 2.4 months vs 15.8 months for the group with signs of Rb), had significantly earlier tumor stage at diagnosis (Even in the absence of genetic testing, screening for children with high risk for Rb is effective in enhancing early diagnosis, improving visual outcome, and increasing eye salvage rate with limited exposure to treatment burden.
Published: 2020

44. How Telemedicine and Centralized Care Changed the Natural History of Retinoblastoma in a Developing Country: Analysis of 478 Patients

Author: Yacoub A, Yousef, Ibrahim, Al-Nawaiseh, Mustafa, Mehyar, Iyad, Sultan, Maysa, Al-Hussaini, Imad, Jaradat, Mona, Mohammad, Reem, AlJabari, Nakhleh, Abu-Yaghi, Carlos, Rodriguez-Galindo, Ibrahim, Qaddoumi, and Matthew, Wilson
Subjects: Male, Time Factors, Retinal Neoplasms, Infant, Newborn, Retinoblastoma, Disease Management, Infant, Combined Modality Therapy, Telemedicine, Child, Preschool, Humans, Female, Developing Countries, Referral and Consultation, Follow-Up Studies, Retrospective Studies
Abstract: To evaluate the efficacy of integrating a telemedicine-based twinning partnership and centralized care for retinoblastoma on survival and eye salvage.Four hundred seventy-eight retinoblastoma patients treated at a tertiary referral cancer center (King Hussein Cancer Centre [KHCC]) from 2003 through 2019.Four hundred seventy-eight retinoblastoma patients treated at KHCC after implementing a telemedicine-based program with St. Jude Children's Research Hospital.We reviewed the outcomes of retinoblastoma patients who were treated at KHCC after implementing a telemedicine-based eye salvage program with St. Jude Children's Research Hospital, and we compared that with outcomes for retinoblastoma patients who were treated before implementing a telemedicine-based retinoblastoma service at KHCC.We analyzed patient demographics, clinical characteristics, treatments received, consultation type and duration, and long-term patient outcomes before and after implementing the twinning program.Over 17 years, 813 eyes from 478 children with retinoblastoma were treated at KHCC. Three hundred thirty-five patients (70%) had bilateral disease. Six patients (4%) with unilateral disease and 66 patients (20%) with bilateral disease had a family history of retinoblastoma. After the twinning program was established in 2003, the mortality rate decreased from 38% to 5% (P 0.0001), and the overall eye salvage rate increased from 4% to 61% (98% for group A, 93% for group B, 81% for group C, and 48% for group D; P 0.0001). Initially, all cases were discussed via telemedicine, but as knowledge transfer increased, the proportion of cases that required discussion decreased to less than 3% 10 years later. Similarly, treatment changes based on consultations decreased from 70% to 7% after 10 years. Both survival and eye-salvage rates were comparable at the early and later stages of implementing the twinning program. At a median follow-up of 120 months, 5% of patients had died of metastases or secondary neoplasms, 81% were alive, and 14% were lost to follow-up.Centralization of care at a single center in developing countries can achieve patient outcomes comparable with those of developed countries via twinning and telemedicine. This benefit can extend to a large region because two thirds of patients treated at KHCC were non-Jordanians.
Published: 2020

45. A Multicenter, International Collaborative Study for American Joint Committee on Cancer Staging of Retinoblastoma: Part II: Treatment Success and Globe Salvage

Author: Ankit Singh, Tomar, Paul T, Finger, Brenda, Gallie, Ashwin, Mallipatna, Tero T, Kivelä, Chengyue, Zhang, Junyang, Zhao, Matthew W, Wilson, Rachel C, Brenna, Michala, Burges, Jonathan, Kim, Vikas, Khetan, Suganeswari, Ganesan, Andrey, Yarovoy, Vera, Yarovaya, Elena, Kotova, Yacoub A, Yousef, Kalle, Nummi, Tatiana L, Ushakova, Olga V, Yugay, Vladimir G, Polyakov, Marco A, Ramirez-Ortiz, Elizabeth, Esparza-Aguiar, Guillermo, Chantada, Paula, Schaiquevich, Adriana, Fandino, Jason C, Yam, Winnie W, Lau, Carol P, Lam, Phillipa, Sharwood, Sonia, Moorthy, Quah Boon, Long, Vera Adobea, Essuman, Lorna A, Renner, Ekaterina, Semenova, Jaume, Català, Genoveva, Correa-Llano, and Elisa, Carreras
Subjects: Adult, Male, Internationality, Adolescent, Retinal Neoplasms, Brachytherapy, Infant, Newborn, Retinoblastoma, Infant, Kaplan-Meier Estimate, Medical Oncology, Eye Enucleation, Radiotherapy, Computer-Assisted, United States, Survival Rate, Young Adult, Treatment Outcome, Child, Preschool, Humans, Female, Registries, Child, Societies, Medical, Neoplasm Staging, Retrospective Studies
Abstract: To evaluate the ability of the American Joint Committee on Cancer (AJCC) 8th edition to predict local tumor control and globe salvage for children with retinoblastoma (RB).International, multicenter, registry-based retrospective case series.A total of 2854 eyes of 2097 patients from 18 ophthalmic oncology centers from 13 countries over 6 continents.International, multicenter, registry-based data were pooled from patients enrolled between January 2001 and December 2013. All RB eyes with adequate records to allow tumor staging by the AJCC 8th edition criteria and follow-up to ascertain treatment outcomes were included.Globe-salvage rates were estimated by AJCC clinical (cTNMH) categories and tumor laterality. Local treatment failure was defined as use of enucleation or external beam radiation therapy (EBRT), with or without plaque brachytherapy or intra-arterial chemotherapy (IAC).Unilateral RB occurred in 1340 eyes (47%). Among the 2854 eyes, tumor categories were cT1 to cT4 in 696 eyes (24%), 1334 eyes (47%), 802 eyes (28%), and 22 eyes (1%), respectively. Of these, 1275 eyes (45%) were salvaged, and 1179 eyes (41%) and 400 eyes (14%) underwent primary and secondary enucleation, respectively. The 2- and 5-year Kaplan-Meier cumulative globe-salvage rates without the use of EBRT by cTNMH categories were 97% and 96% for category cT1a tumors, 94% and 88% for cT1b tumors, 68% and 60% for cT2a tumors, 66% and 57% for cT2b tumors, and 32% and 25% for cT3 tumors, respectively. Risk of local treatment failure increased with increasing cT category (P0.001). Cox proportional hazards regression analysis confirmed a higher risk of local treatment failure in categories cT1b (hazard ratio [HR], 3.5; P = 0.004), cT2a (HR, 15.1; P0.001), cT2b (HR, 16.4; P0.001), and cT3 (HR, 45.0; P0.001) compared with category cT1a. Use of plaque brachytherapy and IAC improved local tumor control in categories cT1a (P = 0.031) and cT1b (P0.001).Multicenter, international, internet-based data sharing validated the 8th edition AJCC RB staging to predict globe-salvage in a large, heterogeneous, real-world patient population with RB.
Published: 2020

46. The role of external beam radiation therapy for retinoblastoma after failure of combined chemoreduction and focal consolidation therapy

Author: Raed Shatnawi, Imad Jaradat, Mona Mohammad, Yacoub A. Yousef, Mustafa Mehyar, Sara Banat, and Ibrahim Al-Nawaiseh
Subjects: Male, medicine.medical_specialty, genetic structures, medicine.medical_treatment, Retinal Neoplasms, External beam radiation, Consolidation therapy, Antineoplastic Combined Chemotherapy Protocols, Medicine, Humans, Stage (cooking), Genetics (clinical), Retrospective Studies, Salvage Therapy, Chemotherapy, Vitreous seeds, Radiotherapy, business.industry, Retinoblastoma, Infant, Dose-Response Relationship, Radiation, medicine.disease, Prognosis, eye diseases, Stage migration, Radiation therapy, Consolidation Chemotherapy, Ophthalmology, Child, Preschool, Pediatrics, Perinatology and Child Health, Female, sense organs, Radiology, business, Follow-Up Studies
Abstract: Purpose: To study the role of external beam radiation therapy (EBRT) for the treatment of retinoblastoma eyes that were not cured by combined systemic chemotherapy and focal consolidation therapy.Methods and Materials: A retrospective case series of 28 eyes for 24 retinoblastoma patients treated by EBRT after the failure of tumor controlled by chemotherapy and focal therapy. The main outcome measures included: international intraocular retinoblastoma classification stage (IIRC) and Reese Ellsworth (RE) stage, tumor seeding, treatment modalities, eye salvage, and survival.Results: The median age at diagnosis was 11 months. There were 14 (58%) males and 20 (83%) bilateral cases. All eyes were treated initially by systemic chemotherapy (range; 6-8 cycles). The dose of radiation used for all eyes was 45 Gray (Gy).The mean follow-up was 75months, and the overall eye salvage rate after EBRT was 13 (46%) eyes: 67% (2/3) for IIRC group B, 71% (5/7) for group C, and 33% (6/18) for group D eyes. Vitreous seeds and tumor stage migration during management by chemotherapy were the most important significant predictive factors for tumor control (p = .001 and 0.033, respectively).Conclusion: Eyes with retinoblastoma that failed chemotherapy followed by focal therapy were controlled with EBRT. However, the presence of vitreous seeds, stage migration during the course of chemotherapy, as well as good vision in the other eye may not justify the known risks of EBRT.
Published: 2020

47. A Multicenter, International Collaborative Study for American Joint Committee on Cancer Staging of Retinoblastoma: Part I: Metastasis-Associated Mortality

Author: Ankit Singh, Tomar, Paul T, Finger, Brenda, Gallie, Ashwin, Mallipatna, Tero T, Kivelä, Chengyue, Zhang, Junyang, Zhao, Matthew W, Wilson, Jonathan, Kim, Vikas, Khetan, Suganeswari, Ganesan, Andrey, Yarovoy, Vera, Yarovaya, Elena, Kotova, Yacoub A, Yousef, Kalle, Nummi, Tatiana L, Ushakova, Olga V, Yugay, Vladimir G, Polyakov, Marco A, Ramirez-Ortiz, Elizabeth, Esparza-Aguiar, Guillermo, Chantada, Paula, Schaiquevich, Adriana, Fandino, Jason C, Yam, Winnie W, Lau, Carol P, Lam, Phillipa, Sharwood, Sonia, Moorthy, Quah Boon, Long, Vera Adobea, Essuman, Lorna A, Renner, Jaume, Català, and Genoveva, Correa-Llano
Subjects: Adult, Male, Internationality, Adolescent, Retinal Neoplasms, Infant, Newborn, Retinoblastoma, Infant, Kaplan-Meier Estimate, Medical Oncology, United States, Survival Rate, Young Adult, Child, Preschool, Humans, Female, Registries, Neoplasm Metastasis, Child, Societies, Medical, Neoplasm Staging, Retrospective Studies
Abstract: To evaluate the ability of the 8th edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual to estimate metastatic and mortality rates for children with retinoblastoma (RB).International, multicenter, registry-based retrospective case series.A total of 2190 patients from 18 ophthalmic oncology centers from 13 countries over 6 continents.Patient-specific data fields for RB were designed and selected by subcommittee. All patients with RB with adequate records to allow tumor staging by the AJCC criteria and follow-up for metastatic disease were studied.Metastasis-related 5- and 10-year survival data after initial tumor staging were estimated with the Kaplan-Meier method depending on AJCC clinical (cTNM) and pathological (pTNM) tumor, node, metastasis category and age, tumor laterality, and presence of heritable trait.Of 2190 patients, the records of 2085 patients (95.2%) with 2905 eyes were complete. The median age at diagnosis was 17.0 months. A total of 1260 patients (65.4%) had unilateral RB. Among the 2085 patients, tumor categories were cT1a in 55 (2.6%), cT1b in 168 (8.1%), cT2a in 197 (9.4%), cT2b in 812 (38.9%), cT3 in 835 (40.0%), and cT4 in 18 (0.9%). Of these, 1397 eyes in 1353 patients (48.1%) were treated with enucleation. A total of 109 patients (5.2%) developed metastases and died. The median time (n = 92) from diagnosis to metastasis was 9.50 months. The 5-year Kaplan-Meier cumulative survival estimates by clinical tumor categories were 100% for category cT1a, 98% (95% confidence interval [CI], 97-99) for cT1b and cT2a, 96% (95% CI, 95-97) for cT2b, 89% (95% CI, 88-90) for cT3 tumors, and 45% (95% CI, 31-59) for cT4 tumors. Risk of metastasis increased with increasing cT (and pT) category (P0.001). Cox proportional hazards regression analysis confirmed a higher risk of metastasis in category cT3 (hazard rate [HR], 8.09; 95% CI, 2.55-25.70; P0.001) and cT4 (HR, 48.55; 95% CI, 12.86-183.27; P0.001) compared with category cT1. Age, tumor laterality, and presence of heritable traits did not influence the incidence of metastatic disease.Multicenter, international, internet-based data sharing facilitated analysis of the 8th edition AJCC RB Staging System for metastasis-related mortality and offered a proof of concept yielding quantitative, predictive estimates per category in a large, real-life, heterogeneous patient population with RB.
Published: 2020

48. Coats’ disease: characteristics, management, outcome, and scleral external drainage with anterior chamber maintainer for stage 3b disease

Author: Robert Rejdak, Rashed Mustafa Nazzal, Adnan H AlAref, Ahmad F Qaroot, Ahmad H ElRimawi, Mona Mohammad, Ibrahim Al-Nawaiseh, Yacoub A. Yousef, Mario Damiano Toro, Katarzyna Nowomiejska, Teresio Avitabile, Omar Abureesh, Yousef, Ya, Elrimawi, Ah, Nazzal, Rm, Qaroot, Af, Alaref, Ah, Mohammad, M, Abureesh, O, Rejdak, R, Nowomiejska, K, Avitabile, T, Toro, Md, and Alnawaiseh, I.
Subjects: Male, Vascular Endothelial Growth Factor A, Visual acuity, genetic structures, medicine.medical_treatment, Visual Acuity, Cryotherapy, leukocoria, Severity of Illness Index, 0302 clinical medicine, 030212 general & internal medicine, Coats' disease, Stage (cooking), Child, Laser Coagulation, General Medicine, medicine.anatomical_structure, Treatment Outcome, 030220 oncology & carcinogenesis, Child, Preschool, Intravitreal Injections, Drainage, Female, Steroids, medicine.symptom, Laser coagulation, Sclera, Research Article, Pars plana, medicine.medical_specialty, Adolescent, Anterior Chamber, coats disease, Leukocoria, Vision Disorders, Observational Study, retinoblastoma, 03 medical and health sciences, Ophthalmology, medicine, Humans, Strabismus, Retrospective Studies, business.industry, Retinal Detachment, Infant, medicine.disease, eye diseases, Retinal Telangiectasis, sense organs, business
Abstract: To report on the characteristics and outcome of management of Coats’ disease, and to describe a novel surgical technique for management of stage 3B with total retinal detachment (RD) by scleral external drainage with anterior chamber (AC-maintainer) placement before the drainage without pars plana vitrectomy. A retrospective study of 26 eyes from 25 Coats’ patients. Outcome measures included: demographics, presentation, laterality, stage, treatment, and outcome. The median age at diagnosis was 3.5 years. Twenty patients (80%) were males, and all except 1 girl had unilateral disease. The presenting complaint was impaired vision in 13 (50%) eyes, leukocoria in 6 (23%) eyes, and strabismus in 7 (27%) eyes. Based on the Shields classification; 3(12%) eyes were stage 1, 9 (35%) eyes were stage 2, 10 (38%) eyes were stage 3, 2 (8%) eyes were stag e4, and 2 (8%) eyes were stage 5. Primary management included cryotherapy (54%), laser photocoagulation (27%), intravitreal anti-vascular endothelial growth factor (23%), intravitreal steroids (23%), and surgical drainage (12%). The 3 eyes in stage 3B (with total exudative RD) underwent subretinal fluid drainage with AC maintainer, and all had the retina reattached completely for 6 months follow up after the surgery. At mean follow up 21 months, 4 (15%) eyes were enucleated, 19 (73%) eyes had improvement or stabilization in visual acuity. Coats’ disease usually presents at advanced stage with poor visual prognosis, individualized management with close follow up are mandatory to save the eye. Subretinal fluid drainage with AC maintainer is a safe and useful technique for repairing total RD in eyes with stage 3B Coats’ disease.
Published: 2020

49. Mutational analysis of the RB1 gene and the inheritance patterns of retinoblastoma in Jordan

Author: Mona Mohammad, Yacoub A. Yousef, Ibrahim Al-Nawaiseh, Rasha Deebajah, Amal Afifi, Mustafa Mehyar, Maysa Al-Hussaini, Ala Saab, Iyad Sultan, Maysa Naji, Imad Jaradat, and Abdelghani Tbakhi
Subjects: Male, Cancer Research, Ubiquitin-Protein Ligases, Genetic counseling, DNA Mutational Analysis, Nonsense mutation, Inheritance Patterns, Genetic Counseling, Biology, medicine.disease_cause, Germline, 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, Germline mutation, Neoplastic Syndromes, Hereditary, Genetics, medicine, Humans, Prospective Studies, Prospective cohort study, Germ-Line Mutation, Genetics (clinical), Sanger sequencing, Mutation, Jordan, Retinoblastoma, Infant, Newborn, High-Throughput Nucleotide Sequencing, Infant, Exons, medicine.disease, Retinoblastoma Binding Proteins, Oncology, Child, Preschool, 030220 oncology & carcinogenesis, 030221 ophthalmology & optometry, symbols, Female
Abstract: Retinoblastoma (RB) is a childhood cancer developing in the retina due to RB1 pathologic variant. Herein we are evaluating the oncogenic mutations in the RB1 gene and the inheritance patterns of RB in the Jordanian patients. In this prospective study, the peripheral blood of 50 retinoblastoma patients was collected, genomic DNA was extracted, mutations were identified using Quantitative multiplex PCR (QM-PCR), Allele-specific PCR, Next Generation Sequencing analysis, and Sanger sequencing. In this cohort of 50 patients, 20(40%) patients had unilateral RB and 30(60%) were males. Overall, 36(72%) patients had germline disease, 17(47%) of whom had the same RB1 pathologic variant detected in one of the parents (inherited disease). In the bilateral group, all (100%) patients had germline disease; 13(43%) of them had inherited mutation. In the unilateral group, 6(30%) had germline disease, 4(20%) of them had inherited mutation. Nonsense mutation generating a stop codon and producing a truncated non-functional protein was the most frequent detected type of mutations (n = 15/36, 42%). Only one (2%) of the patients had mosaic mutation, and of the 17 inherited cases, 16(94%) had an unaffected carrier parent. In conclusion, in addition to all bilateral RB patients in our cohort, 30% of unilateral cases showed germline mutation. Almost half (47%) of germline cases had inherited disease from affected (6%) parent or unaffected carrier (94%). Therefore molecular screening is critical for the genetic counseling regarding the risk for inherited RB in both unilateral and bilateral cases including those with no family history.
Published: 2017
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50. Management outcome(s) in eyes with retinoblastoma previously inadequately treated with systemic chemotherapy alone without focal therapy

Author: Yacoub A, Yousef, Rashed M, Nazzal, Mohammed B, Khalil, Rasha, Deebajah, Mustafa, Mehyar, Shatha, Hajja, Mona, Mohammad, Reem, Al Jabary, Imad, Jaradat, Iyad, Sultan, and Ibrahim, Al Nawaiseh
Subjects: genetic structures, lcsh:Ophthalmology, lcsh:RE1-994, focal therapy, Chemotherapy, vitreous seeds, Original Article, sense organs, eye diseases, retinoblastoma
Abstract: OBJECTIVE: The objective of this study was to evaluate the outcome of management in eyes with intraocular retinoblastoma (RB) that had received inadequate initial therapy (chemotherapy without focal therapy) before eventually receiving necessary consolidation therapy at a tertiary referral center. METHODS: A retrospective observational case series of 30 eyes from 26 RB patients who had initially received systemic chemotherapy as a sole therapy. The main outcome measures were demographics, laterality, International Classification of RB (ICRB), treatments, tumor control, and survival. RESULTS: The median age at diagnosis was 24 months and the median delay between time at diagnosis and time at referral to a tertiary center that has adequate focal therapy for RB was 9.5 months (range 5–20 months). Sixteen (62%) patients were monocular from enucleation of the contralateral eye. Features of ICRB Group A tumors were seen in 3 (10%) eyes, Group B in 7 (23%) eyes, Group C in 2 (7%) eyes, Group D in 16 (53%) eyes, and Group E in 2 (7%) eyes. Eighteen (69%) patients required more systemic chemotherapy (median, 4.4 cycles; range, 2–8 cycles), and 8 (26%) eyes received local chemotherapy (subtenon, intravitreal, or intra-arterial). All treated eyes received consolidation therapy as transpupillary thermotherapy and/or cryotherapy. Radioactive plaque therapy was used in 1 (3%) eye and external beam radiation therapy in 3 (10%) eyes. At a mean follow-up of 13 months (median, 11.5 months; range, 9–27 months), enucleation was avoided in 25 (83%) eyes. Two (7%) eyes were enucleated initially, and 3 (10%) were enucleated after failure of additional therapy. Twenty-three (77%) eyes did not show any viable tumor after a median of 11.5 months of follow-up after the last treatment, and 2 (7%) eyes still have residual tumor recurrences that need more consolidation focal therapy. CONCLUSION: Chemotherapy alone cannot eradicate RB cells in effected eyes without combination with consolidation therapy by a multidisciplinary team to salvage the affected eye as well as its vision. Nonetheless, chemotherapy can be initiated (to keep the tumor at a less invasive stage) for patients from centers or countries where combination therapy is not available until they gain access to adequate management of RB.
Published: 2017

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