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1. A deep learning approach to hard exudates detection and disorganization of retinal inner layers identification on OCT images

Author: Lisa Toto, Anna Romano, Marco Pavan, Dante Degl’Innocenti, Valentina Olivotto, Federico Formenti, Pasquale Viggiano, Edoardo Midena, and Rodolfo Mastropasqua
Subjects: Medicine, Science
Abstract: Abstract The purpose of the study was to detect Hard Exudates (HE) and classify Disorganization of Retinal Inner Layers (DRIL) implementing a Deep Learning (DL) system on optical coherence tomography (OCT) images of eyes with diabetic macular edema (DME). We collected a dataset composed of 442 OCT images on which we annotated 6847 HE and the presence of DRIL. A complex operational pipeline was defined to implement data cleaning and image transformations, and train two DL models. The state-of-the-art neural network architectures (Yolov7, ConvNeXt, RegNetX) and advanced techniques were exploited to aggregate the results (Ensemble learning, Edge detection) and obtain a final model. The DL approach reached good performance in detecting HE and classifying DRIL. Regarding HE detection the model got an AP@0.5 score equal to 34.4% with Precision of 48.7% and Recall of 43.1%; while for DRIL classification an Accuracy of 91.1% with Sensitivity and Specificity both of 91.1% and AUC and AUPR values equal to 91% were obtained. The P-value was lower than 0.05 and the Kappa coefficient was 0.82. The DL models proved to be able to identify HE and DRIL in eyes with DME with a very good accuracy and all the metrics calculated confirmed the system performance. Our DL approach demonstrated to be a good candidate as a supporting tool for ophthalmologists in OCT images analysis.
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. Chemotherapy Induced Corneal Changes Assessed by Corneal Confocal Microscopy: A Review

Author: Eleonora Cosmo, Giulia Midena, Raffaele Parrozzani, and Edoardo Midena
Subjects: cornea, chemotherapy, corneal confocal microscopy, corneal toxicity, peripheral neuropathy, corneal epithelium, Medicine (General), R5-920
Abstract: The eye, and the cornea in particular, is a common site of chemotherapy induced toxicity, and ocular side effects of both traditional and novel agents have been reported. Corneal confocal microscopy (CCM) is an in vivo technique that allows for the study of all the corneal layers in an easy, non-invasive and reproducible way via the direct visualization of corneal cell morphologies as well as of sub-basal nerve plexus. Thus, it represents a useful way to identify and monitor chemotherapy induced corneal alterations. This work aims to review the use of CCM in identifying corneal toxicity secondary to chemotherapy treatment, as regards both corneal nerves alterations in the setting of chemotherapy induced peripheral neuropathy (CIPN) and other corneal structure changes, particularly involving the corneal epithelium.
Published: 2024
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4. Aqueous Humor Cytokines in Idiopathic Epiretinal Membrane: Correlation with Disease Severity

Author: Tommaso Torresin, Angelo Greggio, Rino Frisina, Lorenzo Motta, Irene Gius, Giulia Midena, and Edoardo Midena
Subjects: cytokines, proteomics, epiretinal membrane, aqueous humor, Medicine (General), R5-920
Abstract: Background: To analyze the concentration of aqueous humor (AH) cytokines in eyes with idiopathic epiretinal membrane (iERM) and to investigate their potential correlation with disease severity. Methods: Retrospective cross-sectional case-control institutional study. A total of 16 eyes of 16 iERM patients and 14 eyes of 14 age-matched healthy controls were enrolled. AH samples were analyzed for various biomarkers using a glass-chip protein array. Cytokines associated with inflammation, fibrosis, angiogenesis, and glial signal transduction were quantified. Results: Significant differences in cytokine concentration were observed between the iERM group and controls, with 19 cytokines elevated in the iERM group (among them IL-6, IL-8, PDGF-AB, PDGF-BB, TGFB-1, TGFB-2, TGFB-3, VEGF A, VEGF C, VEGF D, p < 0,05, 95% confidence interval). Correlation analysis revealed associations between cytokine levels and iERM severity. Notably, stages 2, 3, and 4 of iERM demonstrated increased levels of various biomarkers. Conclusions: This study provides insights into the complex molecular interactions underlying iERM pathogenesis, describing a correlation between neuroinflammation and iERM severity.
Published: 2024
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5. Severe retinopathy of prematurity is associated with early post-natal low platelet count

Author: Raffaele Parrozzani, Elisabetta Beatrice Nacci, Silvia Bini, Giulia Marchione, Sabrina Salvadori, Daniel Nardo, and Edoardo Midena
Subjects: Medicine, Science
Abstract: Abstract Pathophysiology of retinopathy of prematurity (ROP) still presents a gap. Lately blood tests parameters of premature infants have been measured at different times of ROP, attempting to detect correlations with ROP development and progression. So far, very early post-natal biomarkers, predictive of ROP outcome, have not been detected. Our purpose is to evaluate, in the earliest post birth blood sample, the correlation between routinely dosed blood parameters and ROP outcome. 563 preterm babies, screened according to ROP guidelines, were included and classified in conformity with ET-ROP study in “Group 1” (ROP needing treatment), “Group 2” (ROP spontaneously regressed) and “noROP” group (never developed ROP). The earliest (within an hour after delivery) blood test parameters routinely dosed in each preterm infant were collected. Platelet count was decreased in Group 1 versus noROP group (p = 0.0416) and in Group 2 versus noROP group (p = 0.1093). The difference of thrombocytopenic infants among groups was statistically significant (p = 0.0071). CRP was higher in noROP versus all ROPs (p = 0.0331). First post-natal blood sample revealed a significant thrombocytopenia in ROP needing treatment, suggesting a role of platelets in the pathophysiology and progression of ROP, possibly considering it as a predictive parameter of ROP evolution.
Published: 2021
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6. Structural and microvascular changes of the peripapillary retinal nerve fiber layer in Von Hippel–Lindau disease: an OCT and OCT angiography study

Author: Elisabetta Pilotto, Elisabetta Beatrice Nacci, Gilda De Mojà, Alfonso Massimiliano Ferrara, Raffaele Parrozzani, Davide Londei, Stefania Zovato, and Edoardo Midena
Subjects: Medicine, Science
Abstract: Abstract Von Hippel–Lindau (VHL) disease is an autosomal dominant genetic disease caused by VHL gene mutation. Retinal hemangioblastomas (RH) are vascularized tumors and represent the main ocular manifestation of the disease. Histopathologically, RH are composed of capillary vessels and stromal cells, the neoplastic population of the lesion. The origin of these stromal cells remains controversial, even if they are hypothesized to be glial cells. The aim of the present study was to investigate neuronal and microvascular changes of the peripapillary retinal nerve fiber layer, in which glial cells, neurons and capillaries (the radial peripapillary capillary plexus) interact. VHL patients with or without peripheral RH were enrolled and compared to healthy controls. Mean peripapillary retinal nerve fiber layer (pRNFL) thickness was measured by means of optical coherence tomography (OCT). The following vascular parameters of the radial peripapillary capillary plexus were quantified using OCT angiography: Vessel Area Density,Vessel Length Fraction, Vessel Diameter Index and Fractal Dimension. One hundred and nine eyes of 61 patients, and 56 eyes of 28 controls were consecutively studied. Mean pRNFL was significantly thinner in VHL eyes without RH versus eyes with RH and controls. Mean pRNFL thickness did not differ between VHL eyes with RH and controls. All OCTA vascular parameters were reduced in VHL eyes with or without RH versus controls, with significative difference for Vessel Diameter Index. The same OCTA parameters did not significantly differ between VHL eyes with or without RH. In VHL eyes without RH, pRNFL thinning may be the consequence of impaired perfusion of the radial peripapillary capillary plexus, while the increase of pRNFL thickness in VHL eyes with RH may depend on possible activation and proliferation of the other RNFL resident cells, the glial cells.
Published: 2021
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7. Hyper-Reflecting Foci in Multiple Sclerosis Retina Associate With Macrophage/Microglia-Derived Cytokines in Cerebrospinal Fluid

Author: Marco Puthenparampil, Tommaso Torresin, Silvia Franciotta, Annachiara Marin, Federica De Napoli, Valentina Annamaria Mauceri, Silvia Miante, Elisabetta Pilotto, Edoardo Midena, and Paolo Gallo
Subjects: multiple sclerosis, OCT, microglia, retina, cerebrospinal fluid, hyper-reflecting foci, Immunologic diseases. Allergy, RC581-607
Abstract: BackgroundIncreasing evidence suggests that retinal hyper-reflecting foci (HRF) might be clusters of activated and proliferating microglia. Since microglia are widespread activated in multiple sclerosis (MS) brain, its evaluation in retina may help to understand and monitor MS-related pathology.AimThis study aims at investigating the association of HRF with cerebrospinal fluid (CSF) cytokines and MRI parameters in relapsing–remitting MS (RRMS).MethodsNineteen RRMS at clinical onset and 15 non-inflammatory neurological disorders (NIND) underwent brain 3T MRI and CSF examination. Optical coherence tomography (OCT) analysis, including HRF count, was performed on RRMS patients. Sixty-nine cytokines/chemokines were analyzed in the CSF by multiplex technology.ResultsIn RRMS, HRF count in the ganglion cell layer (GCL) was associated with IL-1Ra, IL-9, IL-15, IFN-γ, and G-CSF. Moreover, in RRMS patients CSF concentrations of IL-1Ra and G-CSF associated with global cortical thickness. The HRF count in the inner nuclear layer (INL) correlated with IL-22, IL-34, IL-35, CXCL-2, CXCL-10, and CXCL-13, and multivariate analysis confirmed a strong association (r2: 0.47) with both CXCL-2 (β: -0.965, p = 0.0052) and CXCL-13 (β: 0.241, p = 0.018). This latter cytokine increased in RRMS with high HRF count compared with NIND and RRMS with low HRF count. Finally, the CXCL-13/CXCL-2 ratio strongly associated with HRF count (r: 0.8, p < 0.005) and cortical lesion volume (r: 0.5, p < 0.05).ConclusionsThe association of HRF with intrathecally produced monocyte/microglia-derived cytokines confirms their microglial origin and indicates they are worth further evaluating as markers of activated microglia.
Published: 2022
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8. Hyper-reflective retinal foci as possible in vivo imaging biomarker of microglia activation in von Hippel-Lindau disease.

Author: Elisabetta Pilotto, Tommaso Torresin, Maria Laura Bacelle, Gilda De Mojà, Alfonso Massimiliano Ferrara, Stefania Zovato, Giulia Midena, and Edoardo Midena
Subjects: Medicine, Science
Abstract: Purposevon Hippel-Lindau (VHL) disease is caused by a mutation of the VHL gene and characterized by the development of retinal hemangioblastomas (RH). Current pathophysiologic mechanisms of RH development and progression are still insufficient to predict RH behavior. VHL gene is involved in the cellular response to hypoxia and in many intracellular signaling pathways expressed both in angiogenesis and inflammation. Optical coherence tomography (OCT) allows to identify hyper-reflective retinal foci (HRF) known as aggregates of activated microglial cells as possible in vivo biomarker of local inflammation. The aim of the present study was to investigate the presence of HRF in patients with genetically confirmed VHL disease.MethodsIn this cross-sectional study, patients with VHL underwent complete ophthalmological examination and OCT with HRA + OCT Spectralis. HRF were manually identified and calculated in inner (IR), outer (OR) and full retina. Age-matched healthy subjects were enrolled as controls.Results113 eyes of 63 VHL patients and 56 eyes of 28 healthy subjects were evaluated. HRF number was significantly higher in VHL than in controls in IR (28.06 ± 7.50 vs 25.25 ± 6.64, p = 0.042). No difference was observed in OR and in full retina (OR: 7.73 ± 2.59 vs 7.95 ± 2.51, p = 0.599; full retina: 35.79 ± 8.77 vs 33.20 ± 7.47, p = 0.093).ConclusionThe increase of HRF, which mirror retinal microglial activation, characterizes VHL eyes. The role of activated microglia in the retina of VHL eyes needs to be better investigated, mainly considering local VHL disease manifestations.
Published: 2022
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9. OCT Hyperreflective Retinal Foci in Diabetic Retinopathy: A Semi-Automatic Detection Comparative Study

Author: Edoardo Midena, Tommaso Torresin, Erika Velotta, Elisabetta Pilotto, Raffaele Parrozzani, and Luisa Frizziero
Subjects: inflammation, OCT, hyperreflective retinal foci, diabetic retinopathy, automatic detection, biomarker, Immunologic diseases. Allergy, RC581-607
Abstract: Optical coherence tomography (OCT) allows us to identify, into retinal layers, new morphological entities, which can be considered clinical biomarkers of retinal diseases. According to the literature, solitary, small (
Published: 2021
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10. Ocular Side Effects of EGFR-Inhibitor ABT-414 in Recurrent Glioblastoma: A Long-Term Safety Study

Author: Raffaele Parrozzani, Giuseppe Lombardi, Edoardo Midena, Davide Londei, Marta Padovan, Giulia Marchione, Mario Caccese, Giulia Midena, Vittorina Zagonel, and Luisa Frizziero
Subjects: ABT-414, confocal microscopy, cornea, epidermal growth factor receptor-inhibitor, glioblastoma, side effects, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: This study aimed to prospectively evaluate, on a long-term basis, corneal side effects secondary to compassionate administration of epidermal growth factor receptor (EGFR) inhibitor depatuxizumab mafodotin (ABT-414) in patients affected by EGFR-amplified recurrent glioblastoma. Fifteen patients with a median follow-up of 4.3 months after treatment discontinuation were enrolled. Each patient underwent full ophthalmologic examination including in vivo corneal confocal microscopy (CCM). No CTCAE grade 4 toxicity and four (27%) grade 3 toxicities were documented during treatment. Ocular symptoms (blurred vision, eye pain, photophobia) were experienced by all patients, reaching maximal severity after the second ABT-414 infusion, with persistence until treatment discontinuation. During treatment, CCM documented specific changes in the corneal epithelium and in the sub-basal nerve plexus layer fibers of all eyes. The median time of symptoms resolution after treatment discontinuation ranged from 38 days (eye pain) to 53 days (photophobia). The median time of signs resolution ranges from 14 days (corneal ulcer) to 38 days (superficial punctate epitheliopathy, corneal stroma edema and intraepithelial cysts). ABT-414 corneal side effects are detectable in all treated patients. Related symptoms are gradually experienced by all patients during treatment and although reversible, they are characterized by a relative prolonged persistence after treatment discontinuation.
Published: 2020
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11. Corneal side effects induced by EGFR-inhibitor antibody–drug conjugate ABT-414 in patients with recurrent glioblastoma: a prospective clinical and confocal microscopy study

Author: Raffaele Parrozzani, Giuseppe Lombardi, Edoardo Midena, Francesca Leonardi, Davide Londei, Marta Padovan, Mario Caccese, Giulia Marchione, Silvia Bini, Vittorina Zagonel, and Luisa Frizziero
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Background: The aim of this study was to prospectively analyse, for the first time worldwide by in vivo clinical confocal microscopy (CCM), corneal side effects secondary to the use of epidermal growth factor receptor (EGFR) inhibitor depatuxizumab mafodotin (ABT-414) in a cohort of patients affected by EGFR-amplified recurrent glioblastoma. Methods: Each enrolled patient underwent full ophthalmologic examination including in vivo CCM of the cornea. Each patient was examined at baseline and every 2 weeks during treatment as long as patient conditions allowed it. Results: A total of 10 patients were consecutively enrolled. Median follow-up was 5 months. No Common Terminology Criteria for Adverse Events Version 4.0 grade 4 toxicity was documented. Two (20%) grade 3 toxicities were documented at week 8. CCM examination detected in all eyes multiple and diffuse hyperreflective white round spots in the corneal basal epithelial layers (100%), progressive subbasal nerve plexus layer fibres fragmentation followed by full disappearance (100%) and appearance of round cystic structures in the corneal epithelium (100%). All CCM documented side effects reached the peak of prevalence and severity after a median of 3 infusions. After treatment discontinuation, the reversibility of corneal side effects was documented at CCM after a median of 4 weeks. Conclusion: ABT-414 toxicity is not only directed to the corneal epithelium, but also to corneal nerves. Side effects are detectable in all treated patients and CCM documents early corneal epithelium and subbasal nerve plexus toxicity, with subsequent progressive restoration after treatment discontinuation. Ocular side effects due to ABT-414 can be manageable.
Published: 2020
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12. Optical coherence tomography and color fundus photography in the screening of age-related macular degeneration: A comparative, population-based study.

Author: Edoardo Midena, Luisa Frizziero, Tommaso Torresin, Paolo Boscolo Todaro, Giacomo Miglionico, and Elisabetta Pilotto
Subjects: Medicine, Science
Abstract: PURPOSE:To analyze the individual value and the contribution of color fundus photography (CFP) and optical coherence tomography (OCT) in the screening of age-related macular degeneration (AMD) of an unselected population. METHODS:CFP and OCT images of 15957 eyes of 8069 subjects older than 55 years, obtained during a population-based screening for AMD using a single diagnostic non-mydriatic imaging device, were analyzed by a blinded examiner. The two techniques were preliminary evaluated considering the dichotomous parameter "gradable/ungradable", then gradable images were classified. CFP were graded according to the standardized classification of AMD lesions. OCT images were also categorized considering the presence of signs of early/intermediate AMD, late AMD, or other retinal diseases. Another blinded operator re-graded 1978 randomly selected images (for both CFP and OCT), to assess test reproducibility. RESULTS:Of the 15957 eyes, 8356 CFP (52.4%) and 15594 (97.7%) OCT scans were gradable. Moreover, most of the eyes with ungradable CFP (7339, 96.6%) were gradable at OCT. AMD signs were revealed in 7.4% of gradable CFP and in 10.4% of gradable OCT images. Moreover, at OCT, AMD signs were found in 1110 (6.9%) eyes whose CFP were ungradable or without AMD (847 and 263 eyes, respectively). The inter-operator agreement was good for the gradable versus ungradable parameter, and optimal for the AMD grading parameter of CFP. The agreement was optimal for all OCT parameters. CONCLUSIONS:OCT provided gradable images in almost all examined eyes, compared to limited CFP efficiency. Moreover, OCT images allowed to detect more AMD eyes compared to gradable photos. OCT imaging appears to significantly improve the power of AMD screening in a general, unselected population, compared to CFP alone.
Published: 2020
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13. Microscopic Observation of Proliferative Membranes in Fibrocontractive Retinal Disorders

Author: Rino Frisina, Francesco Tessarolo, Ivan Marchesoni, Federico Piccoli, Emiliana Bonomi, Patrizio Caciagli, Edoardo Midena, and Giandomenico Nollo
Subjects: Ophthalmology, RE1-994
Abstract: Proliferative membranes of fibrocontractive retinal disorders are extensively studied from the morphological and evolutive point of view. Despite this, little is known of their cellular composition. In this study, the authors investigated the morphological characteristics and cell composition of various types of surgically excised proliferative membranes and internal limiting membranes (ILMs), in order to provide new data supporting or challenging the pathogenic theories proposed until now. Sixty-nine specimens from 64 eyes of 64 consecutive patients were collected at surgery and subjected to a multilevel analysis by means of optical and electron microscopy. Membrane samples were semiquantitatively evaluated for the amount and distribution of cell nuclei and pigment. Immunohistochemical staining was performed with antibodies to alpha smooth muscle actin and CD68. Data were analyzed after grouping according to the following tissue types: ILM (20 specimens), epiretinal membrane (ERM) (22 specimens), ILM + ERM (20 specimens), and proliferative vitreoretinopathy (PVR) (7 specimens). The cell components found in the ERM specimens, like myofibroblasts, macrophages, and polymorphonuclear cells, were recognized as the expression of cell migration and differentiation that induced an inflammatory process and a fibroproliferative repair process. The detection of pigments in specific types of ERM, like those associated with lamellar macular hole (LMH) or secondary to retinal detachment (RD), diabetes, and PVR, suggested that retinal pigment epithelium (RPE) cells may have a role in the development of these vitreoretinal disorders. The reduction of the ERM cellularity with the patient’s age supports the hypothesis that ERM evolves in time up to a fibrous tissue formation.
Published: 2019
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14. Impact of Baseline Central Retinal Thickness on Outcomes in the VIVID-DME and VISTA-DME Studies

Author: Edoardo Midena, Mark Gillies, Todd A. Katz, Carola Metzig, Chengxing Lu, and Yuichiro Ogura
Subjects: Ophthalmology, RE1-994
Abstract: Purpose. To report the impact of baseline central retinal thickness (CRT) on outcomes in patients with diabetic macular edema (DME) in VIVID-DME and VISTA-DME. Methods. Post hoc analyses of two randomized controlled trials in which 862 DME patients were randomized 1 : 1 : 1 to treatment with intravitreal aflibercept 2.0 mg every 4 weeks (2q4), intravitreal aflibercept 2.0 mg every 8 weeks after five initial monthly doses (2q8), or macular laser photocoagulation at baseline and as needed. We compared visual and anatomical outcomes in subgroups of patients with baseline CRT
Published: 2018
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15. Trans-synaptic degeneration in the optic pathway. A study in clinically isolated syndrome and early relapsing-remitting multiple sclerosis with or without optic neuritis.

Author: Marco Puthenparampil, Lisa Federle, Davide Poggiali, Silvia Miante, Alessio Signori, Elisabetta Pilotto, Francesca Rinaldi, Paola Perini, Maria Pia Sormani, Edoardo Midena, and Paolo Gallo
Subjects: Medicine, Science
Abstract: Increasing evidence suggest that neuronal damage is an early and diffuse feature of Multiple Sclerosis (MS) pathology. Analysis of the optic pathway may help to clarify the mechanisms involved in grey matter damage in MS. Purpose of our study was to investigate the relationship between inflammation and neurodegeneration and to achieve evidence of trans-synaptic degeneration in the optic pathway in MS at clinical onset.50 clinically isolated syndromes/early relapse-onset MS (CIS/eRRMS) with mean disease duration of 4.0±3.5 months, 28 MRI healthy controls (HC) and 31 OCT-HC were studied. Ten patients had optic neuritis at presentation (MSON+), 40 presented with other symptoms (MSON-). MRI examination included 3D-T1, 3D-FLAIR and 3D-DIR sequences. Global cortical thickness (gCTh), pericalcarin CTh (pCTh) and white matter volume (WMV) were analysed by means of Freesurfer on 3D-T1 scans. Optic radiation morphology (OR) and volume (ORV) were reconstructed on the base of the Jülich's Atlas. White matter lesion volume (WMLV), OR-WMLV and percent WM damage (WMLV/WMV = WMLV% and OR-WMLV/ORV = ORWMLV%) were obtained by 3D-FLAIR image segmentation. 3D-DIR sequences were applied to identify inflammatory lesions of the optic nerve. Optic coherence tomography (OCT) protocol included the analysis of global peripapillary retinal nerve fiber layer (g-RNFL) and the 6 fundus oculi's sectors (temporal, T-RNFL; temporal superior, TS-RNFL; nasal superior, NS-RNFL; nasal, N-RNFL; nasal inferior, NI-RNFL, temporal inferior, TI-RNFL). The retina of both eyes was analyzed. The eyes of ON+ were further divided into affected (aON+) or not (naON+).No difference in CTh was found between CIS/eRRMS and HC, and between MSON+ and MSON-. Moreover, MSON+ and MSON- did not differ for any WM lesion load parameter. The most significant correlations between RNFL thickness and optic radiation WM pathology were found in MSON+. In these patients, the temporal RNFL inversely correlated to ipsilateral optic radiation WM lesion load (T-RNFL: r -0.7, p
Published: 2017
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16. Procedural aspects of the organization of the comprehensive European Board of Ophthalmology Diploma examination

Author: Danny G.P. Mathysen, Peter J. Ringens, Edoardo Midena, Artur Klett, Gordana Sunaric-Mégevand, Rafael Martinez-Costa, Denise Curtin, Marie-José Tassignon, Wagih Aclimandos, Catherine Creuzot-Garcher, and Christina Grupcheva
Subjects: disclosure, europe, language, ophthalmology, specialization, Special aspects of education, LC8-6691, Medicine
Abstract: The comprehensive European Board of Ophthalmology Diploma (EBOD) examination is one of 38 European medical specialty examinations. This review aims at disclosing the specific procedures and content of the EBOD examination. It is a descriptive study summarizing the present organization of the EBOD examination. It is the 3rd largest European postgraduate medical assessment after anaesthesiology and cardiology. The master language is English for the Part 1 written test (knowledge test with 52 modified type X multiple-choice questions) (in the past the written test was also available in French and German). Ophthalmology training of minimum 4 years in a full or associated European Union of Medical Specialists (UEMS) member state is a prerequisite. Problem-solving skills are tested in the Part 2 oral assessment, which is a viva of 4 subjects conducted in English with support for native language whenever feasible. The comprehensive EBOD examination is one of the leading examinations organized by UEMS European Boards or Specialist Sections from the point of number of examinees, item banking, and item contents.
Published: 2016
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17. Diabetic Retinopathy in Italy: Epidemiology Data and Telemedicine Screening Programs

Author: Stela Vujosevic and Edoardo Midena
Subjects: Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: In Italy, the number of people living with diabetes is about 3.5 million (5.5% of the population), with an increase by about 60% in the last 20 years and with 1 person out of 3 older than 65 years. The Italian Health Service system estimates that 10 billion euros is spent annually on caring for patients with diabetes, a figure that increases yearly. No national data on prevalence and incidence of legal blindness in patients with diabetes and no national registry of patients with diabetic retinopathy (DR) are currently available. However, the available epidemiological data (in several locations throughout the country) are consistent with those reported in other European countries. The use of telemedicine for the screening of DR in Italy is confined to geographically limited locations. The available data in the literature on implementation and use of telematic screening proved to be successful from patient, caregiver, and authorities point of view. This review addresses the available epidemiological data on DR and telematic screening realities in Italy and thus may help in establishing a national screening program.
Published: 2016
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18. The Nonmydriatic Fundus Camera in Diabetic Retinopathy Screening: A Cost-Effective Study with Evaluation for Future Large-Scale Application

Author: Giuseppe Scarpa, Francesca Urban, Stela Vujosevic, Michele Tessarin, Giovanni Gallo, Annalisa Visentin, Emanuela Foglia, Lucrezia Ferrario, and Edoardo Midena
Subjects: Ophthalmology, RE1-994
Abstract: Aims. The study aimed to present the experience of a screening programme for early detection of diabetic retinopathy (DR) using a nonmydriatic fundus camera, evaluating the feasibility in terms of validity, resources absorption, and future advantages of a potential application, in an Italian local health authority. Methods. Diabetic patients living in the town of Ponzano, Veneto Region (Northern Italy), were invited to be enrolled in the screening programme. The “no prevention strategy” with the inclusion of the estimation of blindness related costs was compared with screening costs in order to evaluate a future extensive and feasible implementation of the procedure, through a budget impact approach. Results. Out of 498 diabetic patients eligible, 80% was enrolled in the screening programme. 115 patients (34%) were referred to an ophthalmologist and 9 cases required prompt treatment for either proliferative DR or macular edema. Based on the pilot data, it emerged that an extensive use of the investigated screening programme, within the Greater Treviso area, could prevent 6 cases of blindness every year, resulting in a saving of €271,543.32 (−13.71%). Conclusions. Fundus images obtained with a nonmydriatic fundus camera could be considered an effective, cost-sparing, and feasible screening tool for the early detection of DR, preventing blindness as a result of diabetes.
Published: 2016
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19. Development and external validation of a prognostic nomogram for metastatic uveal melanoma.

Author: Sara Valpione, Justin C Moser, Raffaele Parrozzani, Marco Bazzi, Aaron S Mansfield, Simone Mocellin, Jacopo Pigozzo, Edoardo Midena, Svetomir N Markovic, Camillo Aliberti, Luca G Campana, and Vanna Chiarion-Sileni
Subjects: Medicine, Science
Abstract: BackgroundApproximately 50% of patients with uveal melanoma (UM) will develop metastatic disease, usually involving the liver. The outcome of metastatic UM (mUM) is generally poor and no standard therapy has been established. Additionally, clinicians lack a validated prognostic tool to evaluate these patients. The aim of this work was to develop a reliable prognostic nomogram for clinicians.Patients and methodsTwo cohorts of mUM patients, from Veneto Oncology Institute (IOV) (N=152) and Mayo Clinic (MC) (N=102), were analyzed to develop and externally validate, a prognostic nomogram.ResultsThe median survival of mUM was 17.2 months in the IOV cohort and 19.7 in the MC cohort. Percentage of liver involvement (HR 1.6), elevated levels of serum LDH (HR 1.6), and a WHO performance status=1 (HR 1.5) or 2-3 (HR 4.6) were associated with worse prognosis. Longer disease-free interval from diagnosis of UM to that of mUM conferred a survival advantage (HR 0.9). The nomogram had a concordance probability of 0.75 (SE .006) in the development dataset (IOV), and 0.80 (SE .009) in the external validation (MC). Nomogram predictions were well calibrated.ConclusionsThe nomogram, which includes percentage of liver involvement, LDH levels, WHO performance status and disease free-interval accurately predicts the prognosis of mUM and could be useful for decision-making and risk stratification for clinical trials.
Published: 2015
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20. New Developments in the Pathophysiology and Management of Diabetic Retinopathy

Author: Ahmed M. Abu El-Asrar, Edoardo Midena, Mohamed Al-Shabrawey, and Ghulam Mohammad
Subjects: Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Published: 2013
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21. Retinal Layers Changes in Human Preclinical and Early Clinical Diabetic Retinopathy Support Early Retinal Neuronal and Müller Cells Alterations

Author: Stela Vujosevic and Edoardo Midena
Subjects: Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: Purpose. To evaluate the changes in thickness of individual inner and outer macular and peripapillary retinal layers in diabetes. Methods. 124 subjects (124 eyes) were enrolled: 74 diabetics and 50 controls. Macular edema, proliferative diabetic retinopathy (DR), any intraocular treatment and refractive error >6 diopters were the main exclusion criteria. Full ophthalmic examination, stereoscopic fundus photography, and spectral domain-OCT were performed. After automatic retinal segmentation (layering) in 5 layers, the thickness of each layer was calculated, and values compared among groups. Results. Thirty patients had no DR, 44 patients had non proliferative DR. A significant increase of inner plexiform and nuclear layers was found in DR eyes versus controls (P
Published: 2013
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22. Hyperreflective Intraretinal Spots in Diabetics without and with Nonproliferative Diabetic Retinopathy: An In Vivo Study Using Spectral Domain OCT

Author: Stela Vujosevic, Silvia Bini, Giulia Midena, Marianna Berton, Elisabetta Pilotto, and Edoardo Midena
Subjects: Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: Purpose. To evaluate the presence of hyperreflective spots (HRS) in diabetic patients without clinically detectable retinopathy (no DR) or with nonproliferative mild to moderate retinopathy (DR) without macular edema, and compare the results to controls. Methods. 36 subjects were enrolled: 12 with no DR, 12 with DR, and 12 normal subjects who served as controls. All studied subjects underwent full ophthalmologic examination and spectral domain optical coherence tomography (SD-OCT). SD-OCT images were analyzed to measure and localize HRS. Each image was analyzed by two independent, masked examiners. Results. The number of HRS was significantly higher in both diabetics without and with retinopathy versus controls (P 0.9). Conclusions. SD-OCT hyperreflective spots are present in diabetic eyes even when clinical retinopathy is undetectable. Their number increases with progressing retinopathy. Initially, HRS are mainly located in the inner retina, where the resident microglia is present. With progressing retinopathy, HRS reach the outer retinal layer. HRS may represent a surrogate of microglial activation in diabetic retina.
Published: 2013
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23. Determinants of Long-Term Survival in Metastatic Choroidal and Ciliary Body Melanoma

Author: Elina S. Rantala, Raffaele Parrozzani, Micaela M. Hernberg, Vanna Chiarion-Sileni, Tero T. Kivelä, Edoardo Midena, Department of Ophthalmology and Otorhinolaryngology, Clinicum, HUS Head and Neck Center, Silmäklinikka, Department of Oncology, HUS Comprehensive Cancer Center, and University of Helsinki
Subjects: Ophthalmology, Uveal melanoma, Patient, Computed-tomography, Genetic evolution, 3125 Otorhinolaryngology, ophthalmology, Mutations
Published: 2023
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24. RADIATION MACULOPATHY IS ANTICIPATED BY OCT HYPERREFLECTIVE RETINAL FOCI

Author: Giulia Midena, Edoardo Midena, Raffaele Parrozzani, Luisa Frizziero, and Giulia Marchione
Subjects: medicine.medical_specialty, medicine.medical_treatment, Brachytherapy, Visual Acuity, Nerve fiber layer, Macular Edema, Iodine Radioisotopes, Macular Degeneration, chemistry.chemical_compound, Retinal Diseases, Optical coherence tomography, Ophthalmology, medicine, Humans, Prospective Studies, Macular edema, Retrospective Studies, medicine.diagnostic_test, business.industry, Retinal, General Medicine, medicine.disease, medicine.anatomical_structure, chemistry, Biomarker (medicine), Maculopathy, business, Tomography, Optical Coherence, Preclinical imaging
Abstract: To investigate, by means of spectral domain optical coherence tomography, retinal reflectivity changes as an early biomarker anticipating radiation-induced macular edema (ME) in patients treated by iodine-125 (I-125) brachytherapy.Thirty patients planned for I-125 brachytherapy because of uveal melanoma were prospectively included and followed every 4 months for five years. Reflectivity alterations, namely hyperreflective retinal foci, were characterized and counted by two independent masked examiners by means of spectral domain optical coherence tomography imaging. Hyperreflective retinal foci were defined as discrete intraretinal reflectivity changes ≤30 µm, with reflectivity similar to nerve fiber layer and without back shadowing.Macular edema occurred in 17 patients (24.2 ±15.1 months) (group 1) after irradiation. Thirteen patients showed no signs of ME at the 5-year follow-up (group 2). The number of hyperreflective retinal foci was statistically higher in sequential visits until the evidence of ME in group 1 vs group 2 (P0.0001). In group 1, hyperreflective retinal foci at the follow-up before the evidence of ME were significantly related to the OCT central subfield thickness at ME appearance (P = 0.0002, r2=0.6129). The intergrader agreement was almost perfect (intraclass correlation coefficient = 0.80).Hyperreflective retinal foci may be considered as an early in vivo imaging biomarker of retinal inflammatory response to ocular irradiation, anticipating the development of radiation maculopathy.
Published: 2022
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25. Comparison of 50° handheld fundus camera versus ultra-widefield table-top fundus camera for diabetic retinopathy detection and grading

Author: Edoardo Midena, Luca Zennaro, Cristian Lapo, Tommaso Torresin, Giulia Midena, and Luisa Frizziero
Subjects: Ophthalmology
Published: 2023

26. EFFICACY AND SAFETY OF INTRAVITREAL AFLIBERCEPT USING A TREAT-AND-EXTEND REGIMEN FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION

Author: Thomas Schmelter, Edoardo Midena, Paul Mitchell, Helmut Allmeier, Frank G. Holz, Philip G Hykin, Aries study investigators, Sebastian Wolf, George N. Lambrou, and Eric H Souied
Subjects: Male, Vascular Endothelial Growth Factor A, medicine.medical_specialty, Time Factors, Visual acuity, Recombinant Fusion Proteins, Visual Acuity, Angiogenesis Inhibitors, 030204 cardiovascular system & hematology, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Ranibizumab, Ophthalmology, Age related, Humans, Medicine, Macula Lutea, Dosing, Aged, Aflibercept, Aged, 80 and over, business.industry, General Medicine, Middle Aged, Macular degeneration, medicine.disease, Confidence interval, Regimen, Receptors, Vascular Endothelial Growth Factor, Treatment Outcome, Intravitreal Injections, Wet Macular Degeneration, 030221 ophthalmology & optometry, Female, medicine.symptom, business, Tomography, Optical Coherence, Follow-Up Studies, medicine.drug
Abstract: Treating neovascular age-related macular degeneration with intravitreal aflibercept treat-and-extend (TE) can reduce treatment burden. ARIES assessed whether intravitreal aflibercept early-start TE was noninferior to late-start TE.A randomized, open-label, Phase 3b/4 study that included treatment-naïve patients aged ≥50 years with the best-corrected visual acuity 73-25 Early Treatment Diabetic Retinopathy Study letters and active choroidal neovascularization secondary to AMD. Patients received 2 mg intravitreal aflibercept at Week (W) 0, W4, W8, and W16. At W16, patients were randomized 1:1 to early-start (2W interval adjustments) or late-start TE (8W intervals until W48 then 2W interval adjustments). Primary endpoint: the best-corrected visual acuity change from randomization to W104.Two-hundred seventy-one patients were randomized. The mean (SD) best-corrected visual acuity at baseline was 60.2 (12.1; early-TE) and 61.3 (10.8; late-TE) letters. The mean (SD) best-corrected visual acuity change (W16-104) was -2.1 (11.4) versus -0.4 (8.4) letters (early-TE vs. late-TE; least-squares mean difference: -2.0; 95% confidence interval: -4.75 to 0.71; P = 0.0162 for noninferior); +4.3 (13.4) versus +7.9 (11.9) letters (W0-104). The mean (SD) number of injections was 12.0 (2.3) versus 13.0 (1.8). From baseline to W104, 93.4% and 96.2% maintained best-corrected visual acuity; the mean (SD) central retinal thickness change was -161.6 (135.6) µm and -158.6 (125.1) µm. The last injection interval (W104) was ≥12W for 47.2% and 51.9% of patients.Outcomes were similar between patients with neovascular age-related macular degeneration treated with an intravitreal aflibercept early-TE or late-TE regimen after initial dosing, with one injection difference over 2 years.ClinicalTrials.gov Identifier: NCT02581891 https://clinicaltrials.gov/ct2/show/NCT02581891. Supplemental Digital Contents (files 1 http://links.lww.com/IAE/B419).
Published: 2021
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27. Intraocular fluid biomarkers (liquid biopsy) in human diabetic retinopathy

Author: Elisabetta Pilotto, Edoardo Midena, Giulia Midena, and Luisa Frizziero
Subjects: 0301 basic medicine, Proteomics, medicine.medical_specialty, genetic structures, Eye disease, Aqueous humor, Diabetes, Diabetic macular edema, Diabetic retinopathy, Liquid biopsy, Metabolomics, Vitreous, Aqueous Humor, Biomarkers, Humans, Liquid Biopsy, Diabetes Mellitus, Diabetic Retinopathy, Macular Edema, Review Article, 03 medical and health sciences, Cellular and Molecular Neuroscience, chemistry.chemical_compound, 0302 clinical medicine, Ophthalmology, Diabetes mellitus, medicine, Sampling (medicine), business.industry, Retinal, Precision medicine, medicine.disease, Sensory Systems, eye diseases, 030104 developmental biology, chemistry, Intraocular fluid, 030221 ophthalmology & optometry, sense organs, business
Abstract: Purpose This article aims to review the impact of detecting and quantifying intraocular biomarkers (liquid biopsy) in both aqueous and vitreous humor in eyes of people affected by diabetes mellitus. Methods This is a detailed review about aqueous and/or vitreous humor sampling in human diabetic eyes for proteomic and/or metabolomic analysis contributing to the understanding of the pathophysiology and treatment effects of diabetic retinopathy. Results Aqueous and vitreous humor molecular biomarkers proved to be directly correlated to each other and valuable to study retinal conditions. Moreover, proteomic and metabolomic analysis showed that the biomarkers of neuroinflammation, neurodegeneration, and vasculopathy are detectable in intraocular fluids and that their concentration changes in different stages of disease, and in response to treatment of all diabetic retinopathy aspects, mainly diabetic macular edema and proliferative retinopathy. Conclusions Liquid biopsy offers the possibility to improve our knowledge of intraocular eye disease induced by diabetes mellitus. The exact quantification of intraocular biomarkers contributes to the precision medicine approach even in the diabetic retinopathy scenario. The diffusion of this approach should be encouraged to have quantifiable information directly from the human model, which may be coupled with imaging data.
Published: 2021

28. Two novel compound heterozygous SAG mutations in an Italian patient with Oguchi disease: A genetic and multimodal retinal imaging study

Author: Eva Trevisson, Elisabetta Pilotto, Francesca Guidolin, Evelyn Longhin, Elisabetta Beatrice Nacci, and Edoardo Midena
Subjects: 0301 basic medicine, Pathology, medicine.medical_specialty, genetic structures, Fundus (eye), Compound heterozygosity, Frameshift mutation, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, medicine, congenital stationary night blindness, Congenital stationary night blindness, medicine.diagnostic_test, business.industry, Oguchi disease, SAG gene, Mizuo Nakamura phenomenon, OCT, Retinal, General Medicine, medicine.disease, Ophthalmology, 030104 developmental biology, chemistry, 030221 ophthalmology & optometry, sense organs, business, Erg, Electroretinography
Abstract: Background: Oguchi disease is a rare autosomal recessive retinal dystrophy, characterized by congenital stationary blindness and caused by pathogenic variants in SAG and GRK1 genes. The present study aimed to report an Italian patient affected by Oguchi disease, evaluated by means of a multimodal retinal imaging study and harboring two novel heterozygous pathogenic variants in the SAG gene. Materials and methods: A 60-year-old female complaining congenital stationary night blindness was investigated through fundus photograph, optical coherence tomography (OCT), electroretinography (ERG), and genetic testing. Results: Fundus examination showed a golden-grayish fundus aspect. The rod response of the scotopic ERG was undetectable and mixed rod-cone response was electronegative. Fundus photographs obtained in light and in prolonged dark-adapted conditions allowed to detect the Mizuo-Nakamura phenomenon. Light condition OCT over the abnormal retinal regions showed high-intensity areas in the outer photoreceptor segment layer, that reduced with prolonged dark adaption. Genetic testing identified two rare heterozygous sequence variants in the SAG gene: NM_000541.5:c.807delA p.(Glu270Lysfs*9) and NM_000541.5:c.1047-1G>C confirming the diagnosis of Oguchi disease. Conclusions: We identified the first Italian compound heterozygous patient harboring two novel alterations in the SAG gene (a frameshift deletion and a splicing variant). The involvement of the SAG gene in Oguchi disease is a common finding in Japanese population, but rarely identified in Caucasians. Clinical suspicion should prompt the molecular analysis of genes associated with this condition.
Published: 2021
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29. Correction to: Refractory full thickness macular hole: current surgical management

Author: Rino Frisina, Irene Gius, Luigi Tozzi, and Edoardo Midena
Subjects: Ophthalmology, Treatment Outcome, Vitrectomy, Visual Acuity, Correction, Humans, Epiretinal Membrane, Retinal Perforations, Basement Membrane, Tomography, Optical Coherence, Retrospective Studies
Abstract: This review aims to collect the proposed surgical techniques for treating full thickness macular hole (FTMH) refractory to pars plana vitrectomy and internal limiting membrane (ILM) peeling and to analyse and compare anatomical and functional outcomes in order to evaluate their efficacy. The articles were grouped according to the surgical techniques used. Refractory FTMH closure rate and best-corrected visual acuity (BCVA) gain were the two analysed parameters. Thirty-six articles were selected. Ten surgical technique subgroups were defined: autologous platelet concentrate (APC); lens capsular flap transplantation (LCFT); autologous free ILM flap transplantation (free ILM flap); enlargement of ILM peeling, macular hole hydrodissection (MHH), autologous retinal graft (ARG), silicon oil (SO), human amniotic membrane (hAM), perifoveal relaxing retinotomy, arcuate temporal retinotomy. Refractory FTMH closure rate was similar among subgroups, not significant heterogeneity emerged (p = 0.176). BCVA gain showed a significant dependence on surgical technique (p 0.0001), significant heterogeneity among subgroups emerged (p 0.0001). Three sets of surgical technique subgroups with a homogeneous BCVA gain were defined: high BCVA gain (hAM); intermediate BCVA gain (APC, ARG, LCFT, MHH, SO); low BCVA gain (free ILM flap, enlargement of peeling, arcuate temporal retinotomy). In terms of visual recovery, the most efficient technique for treating refractory FTMH is hAM, lens capsular flap and APC that allow to obtain better functional outcomes than free ILM flap. MHH, ARG, perifoveal relaxing and arcuate temporal retinotomy require complex and unjustified surgical manoeuvres in view of the surgical alternatives with overlapping anatomical and functional results.难治性全层黄斑裂孔的手术治疗现状: 摘要: 本综述旨在总结玻璃体切除术和内界膜剥离术在处理难治性全层黄斑裂孔(FTMH)中的手术技巧, 分析并比较术后解剖和功能的不同, 以评估其疗效。本文根据已有的手术技术进行分组。以难治性FTMH的闭合率和最佳矫正视力(BCVA)的提高为2个分析指标。本综述共纳入36篇文献。手术技术分为10个亚组: 自体血小板浓缩(APC)、晶状体囊膜瓣移植(LCFT)、自体游离ILM瓣移植(游离ILM瓣)、ILM扩大剥离、黄斑裂孔水分离(MHH)、自体视网膜移植(ARG)、硅油(SO)、人羊膜(hAM)移植、中心凹周围区松解视网膜切开术、弧形颞侧视网膜切开术。各亚组间难治性FTMH闭合率相似, 未出现明显的异质性(p 0.176)。最佳矫正视力的获益与手术技术有显著的相关性(p 0.0001), 各亚组间也存在明显的异质性(p 0.0001)。各种手术技术根据BCVA的获益定义为三个亚组: 高BCVA获益(hAM)、中等BCVA获益(APC、ARG、LCFT、MHH、SO)和低BCVA获益(游离ILM皮瓣、ILM扩大剥离、弧形颞侧视网膜切开术)。就视力恢复而言, 治疗难治性FTMH最有效的技术是hAM。与游离ILM皮瓣相比, LCF和APC可获得更佳的功能性恢复。针对各种手术方案具有重叠交叉的解剖和功能结果, MHH、ARG、中心凹周围区松解和弧形颞侧视网膜切开术需要复杂和未得到验证的手术操作。.
Published: 2022
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30. Corneal Confocal Microscopy as a Quantitative Imaging Biomarker of Diabetic Peripheral Neuropathy: A Review

Author: Eleonora Cosmo, Giulia Midena, Luisa Frizziero, Marisa Bruno, Michela Cecere, and Edoardo Midena
Subjects: diabetes, diabetic peripheral neuropathy, corneal confocal microscopy, General Medicine
Abstract: Distal symmetric polyneuropathy (DPN), particularly chronic sensorimotor DPN, represents one of the most frequent complications of diabetes, affecting 50% of diabetic patients and causing an enormous financial burden. Whilst diagnostic methods exist to detect and monitor this condition, they have significant limitations, mainly due to their high subjectivity, invasiveness, and non-repeatability. Corneal confocal microscopy (CCM) is an in vivo, non-invasive, and reproducible diagnostic technique for the study of all corneal layers including the sub-basal nerve plexus, which represents part of the peripheral nervous system. We reviewed the current literature on the use of CCM as an instrument in the assessment of diabetic patients, particularly focusing on its role in the study of sub-basal nerve plexus alterations as a marker of DPN. CCM has been demonstrated to be a valid in vivo tool to detect early sub-basal nerve plexus damage in adult and pediatric diabetic patients, correlating with the severity of DPN. Despite its great potential, CCM has still limited application in daily clinical practice, and more efforts still need to be made to allow the dissemination of this technique among doctors taking care of diabetic patients.
Published: 2022

31. Determinants of Long-Term Survival in Metastatic Choroidal and Ciliary Body Melanoma: Long-Term Survival in Metastatic Ciliochoroidal Melanoma

Author: Elina S, Rantala, Raffaele, Parrozzani, Micaela M, Hernberg, Vanna, Chiarion-Sileni, Tero T, Kivelä, and Edoardo, Midena
Abstract: To build and validate a prognostic model that predicts long-term overall survival (OS) in metastatic choroidal and ciliary body melanoma (CCBM) to facilitate patient counseling and planning, reporting, and interpreting clinical trials.Retrospective cohort study with validation.We analyzed predictors of intermediate (IMT; 25-42 months) and long-term (LT; ≥42 months) OS in a Finnish nationwide cohort of 330 patients with metastatic CCBM. Short-term (25 months), IMT and LT survival were compared with pairwise and ordinal logistic regression. A single-center cohort of 259 patients from Italy was used for validation. Models were compared with deviance test.Median OS was 12 and 17 months in the building and validation dataset, respectively; 40 (12%) and 31 (9%) as compared to 44 (17%) and 32 (12%) patients were IMT and LT survivors, respectively. Alkaline phosphatase (AP) or lactate dehydrogenase (LD) level never exceeded 2 x upper normal limit (UNL) in either LT cohort. Conditional to both being ≤2 x UNL, distant metastasis-free interval (DMFI)42 months (OR 4.09-4.64; p.001) paired with age60 years (OR 3.23, p=.002), having no symptoms (OR 4.19, p=.005), and the largest diameter of the largest metastasis30 mm (TNM M1a; OR 3.05, p=.001) independently predicted higher odds of surviving longer (IMT or LT) without model preference. These results were confirmed in the validation dataset.AP or LD2 x UNL essentially precluded LT survival. The most robust predictor otherwise was DMFI42 months, followed by age60 years, absence of symptoms, and TNM M1a.
Published: 2022

32. The Narrative Medicine Approach in the Treatment of Diabetic Macular Edema: An Italian Experience

Author: Edoardo Midena, Chiara Polo, Luisa Frizziero, Maria Giulia Marini, Rosangela Lattanzio, Maria Vadalà, Elisabetta Pilotto, Monica Varano, Midena, Edoardo, Polo, Chiara, Frizziero, Luisa, Marini, Maria Giulia, Lattanzio, Rosangela, Vadala',Maria, Pilotto, Elisabetta, and Varano, Monica
Subjects: Diabetic Retinopathy, diabetes, Settore MED/30 - Malattie Apparato Visivo, Health, Toxicology and Mutagenesis, Public Health, Environmental and Occupational Health, Narrative Medicine, Macular Edema, caregiver, diabetic macular edema, narrative medicine, patient’s journey, quality of life, Humans, Intravitreal Injections, Quality of Life, Diabetes Mellitus
Abstract: The study retraces the healthcare pathway of patients affected by diabetic macular edema (DME) through the direct voice of patients and caregivers by using a “patient journey” and narrative method approach. The mapping of the patient’s journey was developed by a multidisciplinary board of health professionals and involved four Italian retina centers. DME patients on intravitreal injection therapy and caregivers were interviewed according to the narrative medicine approach. Narratives were analyzed through a quali-quantitative tool, as set by the narrative medicine method. The study involved four specialized retina centers in Italy and collected a total of 106 narratives, 82 from DME patients and 24 from caregivers. The narratives reported their difficulty in identifying the correct pathway of care because of a limited awareness of diabetes and its complications. Patients experienced reduced autonomy due to ocular complications. In the treatment of diabetes and its complications, a multidisciplinary approach currently appears to be missing. DME reduces the quality of life of affected patients. The narrative medicine approach offers qualitative and emotional patient-guided information. The patient journey provides all of those involved in the management of DME with flowcharts to refer to, identifying the critical points in the healthcare journey of DME patients to improve the management of the disease.
Published: 2022

33. Standardization of Optical Coherence Tomography Angiography Imaging Biomarkers in Diabetic Retinal Disease

Author: Olga Simó-Servat, Peter H Scanlon, Rafael Simó, Anat Lowenstein, João Figueira, Maria H. Madeira, Recivall Pascuall Salongcay, Ana Rita Santos, Tunde Peto, António C.-V. Martinho, Mariacristina Parravano, Cristina Hernández, José Cunha-Vaz, Edoardo Midena, Stela Vujosevic, Inês Marques, Dinah Zur, and Repositório Científico do Instituto Politécnico do Porto
Subjects: medicine.medical_specialty, Diabetic retinal disease, Imaging biomarkers, OCT angiography, Standardization of terminology, genetic structures, Disease, Cellular and Molecular Neuroscience, chemistry.chemical_compound, SDG 3 - Good Health and Well-being, Artificial Intelligence, Diabetes Mellitus, medicine, Humans, Fluorescein Angiography, Diabetic Retinopathy, business.industry, Retinal Vessels, Retinal, General Medicine, Optical coherence tomography angiography, Reference Standards, RA645.D54, eye diseases, Sensory Systems, Ophthalmology, chemistry, RE, sense organs, Radiology, business, Biomarkers, Tomography, Optical Coherence
Abstract: Optical coherence tomography Angiography (OCT-A) represents a revolution in the noninvasive evaluation of retinal and choroidal circulation especially in detecting early clinical signs of diabetic retinal disease (DRD). With appropriate use, OCT-A characteristics and measurements have the potential to become new imaging biomarkers in managing and treating DRD. Major challenges include (a) provision of standardized outputs from different OCT-A instruments providing standardized terminology to correctly interpret data; (b) the presence of artifacts; (c) the absence of standardized grading or interpretation method in the evaluation of DRD, similar to that already established in fundus photography; and (d) establishing how OCT-A might be able to provide surrogate markers to demonstrate blood retinal barrier breakdown and vascular leakage, commonly associated with DRD. In fact, OCT-A guidelines for DRD are still evolving. The outputs of quantitative OCT-A data offer a unique opportunity to develop tools based on artificial intelligence to assist the clinicians in diagnosing, monitoring, and managing patients with diabetes. In addition, OCT-A has the potential to become a useful tool for the evaluation of cardiovascular diseases and different neurological diseases including cognitive impairment. This article written by the members of Diabetic Retinopathy expert committee of the European Vision Clinical Research network will review the available evidence on the use of OCT-A as an imaging biomarker in DRD and discuss the limits and the current application as well as future developments for its use in both clinical practice and research trials of DRD.
Published: 2021
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34. A possible strategic role of air during pars plana vitrectomy for macula-involving rhegmatogenous retinal detachment

Author: Luigi Tozzi, Rino Frisina, Giuseppe Frascogna, Irene Gius, Edoardo Midena, Tobia Pizzolon, and Angelo Greggio
Subjects: Pars plana, Subretinal fluid, Intraocular pressure, medicine.medical_specialty, genetic structures, Macula-involving rhegmatogenous retinal detachment, medicine.medical_treatment, Visual Acuity, Vitrectomy, 03 medical and health sciences, 0302 clinical medicine, Ophthalmology, medicine, Humans, Macula Lutea, Air, Retinal fold, Vitreous cutter port, Retrospective Studies, business.industry, Retinal Detachment, Lens Status, Retinal detachment, Cataract surgery, medicine.disease, eye diseases, medicine.anatomical_structure, 030221 ophthalmology & optometry, sense organs, Tamponade, business, 030217 neurology & neurosurgery
Abstract: To evaluate the advantages and safety of vitrectomy under air for treating macula-involving rhegmatogenous retinal detachment (RRD). Consecutive patients with macula-involving RRD who underwent vitrectomy under air were recruited. Demographic and clinical data were: age, gender, eye, lens status, best corrected visual acuity (BCVA) in logarithm of the minimum angle of resolution (logMAR), axial length, intraocular pressure (IOP). RRD parameters were: RRD extent, retinal breaks number. Surgical data were: cataract surgery, tamponade used. Postoperative parameters were: BCVA, IOP at first, third, sixth month, recurrent RD, incidence of retinal folds, subretinal fluid (SRF) persistence, macular displacement. Seventy-one eyes (71 patients) were recruited. Cataract surgery was performed in 32 of 45 phakic patients. The tamponade used was: sulfur hexafluoride 18% (41), silicon oil (SO) (26), high-density SO (4). BCVA improved significantly from baseline (1.2 ± 0.4 logMAR) to the last control (0.8 ± 0.7 logMAR) (P = 0.03285). Recurrent RD incidence was 14.1%. Postoperative complications were: retinal folds (2), SRF persistence (3), macular displacement (2). Vitrectomy under air is a safe alternative technique for treating macula-involving RRD. Vitrectomy under air allows surgeon to remove accurately the vitreous from the peripheral retina and facilitates the removal of SRF reducing the complications related to its postoperative persistence.
Published: 2020
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35. Quantification of vascular and neuronal changes in the peripapillary retinal area secondary to diabetic retinopathy

Author: Luisa Frizziero, Edoardo Midena, Raffaele Parrozzani, Davide Londei, and Elisabetta Pilotto
Subjects: medicine.medical_specialty, Retina, Imaging, Cellular and Molecular Neuroscience, chemistry.chemical_compound, Oct angiography, Optical coherence tomography, Ophthalmology, Healthy control, medicine, Humans, Fluorescein Angiography, Inflammation, Optic Nerve, Diabetic Retinopathy, medicine.diagnostic_test, business.industry, Retinal Vessels, Retinal, Diabetic retinopathy, medicine.disease, eye diseases, Sensory Systems, Ganglion, Cross-Sectional Studies, medicine.anatomical_structure, chemistry, Optic nerve, business, Tomography, Optical Coherence
Abstract: PurposeTo investigate and quantify peripapillary vascular and neuronal changes secondary to diabetic retinopathy, using spectral-domain optical coherence tomography (OCT) and OCT angiography (OCTA).DesignThis was a cross-sectional study.Methods51 eyes of 51 patients affected by non-proliferative diabetic retinopathy (NPDR) and 19 age-matched healthy control eyes underwent full ophthalmic examination, including OCT and OCTA in the peripapillary area. Vessel area density (VAD), vessel length fraction (VLF) and vessel diameter index (VDI) were quantified in a ring-shaped region of interest of each OCTA image. Capillaries and larger vessels were separately analysed. The thickness of the peripapillary retinal nerve fibre layer (pRNFL) and macular ganglion cell complex (GCC) was also analysed.ResultsVAD and VLF of peripapillary capillaries were significantly reduced in NPDR eyes, along with the progression of NPDR (pConclusionsRetinal capillary remodelling in NPDR involves the peripapillary vascularisation too, as confirmed by OCTA quantitative parameters. The peripapillary macrovasculature and microvasculature need to be separately evaluated. The lack of direct correlation between peripapillary capillaries changes and the loss of retinal nerve fibres suggests that neuronal damage cannot be simply considered secondary to the microvascular one.
Published: 2020
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36. Validation of an Automated Artificial Intelligence Algorithm for the Quantification of Major OCT Parameters in Diabetic Macular Edema

Author: Edoardo Midena, Lisa Toto, Luisa Frizziero, Giuseppe Covello, Tommaso Torresin, Giulia Midena, Luca Danieli, Elisabetta Pilotto, Michele Figus, Cesare Mariotti, and Marco Lupidi
Subjects: diabetic macular edema, artificial intelligence, biomarker, spectral domain OCT, outcomes, subretinal fluid, intraretinal fluid, hyperreflective retinal foci, external limiting membrane, ellipsoid zone, General Medicine
Abstract: Artificial intelligence (AI) and deep learning (DL)-based systems have gained wide interest in macular disorders, including diabetic macular edema (DME). This paper aims to validate an AI algorithm for identifying and quantifying different major optical coherence tomography (OCT) biomarkers in DME eyes by comparing the algorithm to human expert manual examination. Intraretinal (IRF) and subretinal fluid (SRF) detection and volumes, external limiting-membrane (ELM) and ellipsoid zone (EZ) integrity, and hyperreflective retina foci (HRF) quantification were analyzed. Three-hundred three DME eyes were included. The mean central subfield thickness was 386.5 ± 130.2 µm. IRF was present in all eyes and confirmed by AI software. The agreement (kappa value) (95% confidence interval) for SRF presence and ELM and EZ interruption were 0.831 (0.738–0.924), 0.934 (0.886–0.982), and 0.936 (0.894–0.977), respectively. The accuracy of the automatic quantification of IRF, SRF, ELM, and EZ ranged between 94.7% and 95.7%, while accuracy of quality parameters ranged between 99.0% (OCT layer segmentation) and 100.0% (fovea centering). The Intraclass Correlation Coefficient between clinical and automated HRF count was excellent (0.97). This AI algorithm provides a reliable and reproducible assessment of the most relevant OCT biomarkers in DME. It may allow clinicians to routinely identify and quantify these parameters, offering an objective way of diagnosing and following DME eyes.
Published: 2023
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37. Retinal Hyperreflecting Foci Associate With Cortical Pathology in Multiple Sclerosis

Author: Marta Pengo, Silvia Miante, Silvia Franciotta, Marta Ponzano, Tommaso Torresin, Francesca Bovis, Francesca Rinaldi, Paola Perini, Martina Saiani, Monica Margoni, Alessandra Bertoldo, Maria Pia Sormani, Elisabetta Pilotto, Edoardo Midena, Paolo Gallo, and Marco Puthenparampil
Subjects: Multiple Sclerosis, Relapsing-Remitting, Humans, Retina, Tomography, Optical Coherence, Multiple Sclerosis, Optic Neuritis, Neurology, Optical Coherence, Neurology (clinical), Relapsing-Remitting, Tomography
Abstract: Background and ObjectivesMicroglia, the resident immune cell of the brain and retina, is widespread activated in the white and gray matter (GM) in multiple sclerosis (MS). The objective of this study is to evaluate the presence and number of hyperreflecting foci (HRF), considered clusters of activated and proliferating retinal microglia, and their association with clinical and radiologic disease parameters in relapsing-remitting MS (RRMS).MethodsAt baseline, 80 patients with RRMS underwent optical coherence tomography (OCT) and 3T-MRI (including 3-dimensional T1, fluid-attenuated inversion recovery, and double inversion recovery sequences), closed to their disease onset (6.3 ± 5.1 months). These patients were then clinically and radiologically followed up for a mean of 43 months, evaluating the no evidence of disease activity (NEDA) condition, further divided into clinical (cNEDA) and radiologic (rNEDA). Patients with a clinical history or MRI/OCT findings suggestive of optic neuritis (ON) were excluded from the study.ResultsCompared with healthy controls, the HRF number was significantly higher in the inner nuclear layer (INL) of patients with RRMS (19.55 ± 5.65 vs 13.84 ± 2.57, p < 0.001) and associated with INL volume (β: 1.21, p < 0.001). GM lesion volume significantly correlated with the INL HRF count (p = 0.008). Survival analysis revealed a significant association between INL HRF and both cNEDA (p = 0.017) and rNEDA (p = 0.002).DiscussionWe found a strong association between retinal microglial proliferation and cortical pathology in RRMS, a finding suggesting a possible underlying common immunopathologic mechanism. Furthermore, microglial activation at baseline was observed to predict subsequent inflammatory events, indicating that HRF might be a candidate prognostic biomarker worthy of further investigation.Classification of EvidenceThis study provides Class II evidence that in patients with early RRMS but without ON, the number of HRF on OCT of the retinal inner nuclear layer is associated with cNEDA and rNEDA.
Published: 2022

38. Effect of COVID-19-related lockdown on ophthalmic practice in Italy: A report from 39 institutional centers

Author: Roberto dell’Omo, Mariaelena Filippelli, Gianni Virgili, Francesco Bandello, Giuseppe Querques, Paolo Lanzetta, Teresio Avitabile, Francesco Viola, Michele Reibaldi, Francesco Semeraro, Luciano Quaranta, Stanislao Rizzo, Edoardo Midena, Giuseppe Campagna, Ciro Costagliola, Paola Marolo, Carlo Enrico Traverso, Michele Iester, Carlo Alberto Cutolo, Claudio Azzolini, Simone Donati, Elias Premi, Paolo Nucci, Stela Vujosevic, Giovanni Staurenghi, Ferdinando Bottoni, Francesco Romano, Domenico Grosso, Enrico Borrelli, Riccardo Sacconi, Paolo Milella, Simone Ganci, Mario R. Romano, Gabriella Ricciardelli, Davide Allegrini, Marco Casaluci, Davide Romano, Giorgio Marchini, Francesca Chemello, Camilla Amantea, Rino Frisina, Elisabetta Pilotto, Raffaele Parrozzani, Daniele Veritti, Valentina Sarao, Tognetto Daniele, Massimo Busin, Francesco Parmeggiani, Katia De Nadai, Luca Furiosi, Rodolfo Mastropasqua, Bruno Battaglia, Matteo Gironi, Stefano Gandolfi, Enrico Luciani, Paolo Mora, Costantino Schiavi, Patrizia Bertaccini, Alessandro Finzi, Matilde Roda, Carlo Cagini, Marco Lupidi, Fabrizio Giansanti, Daniela Bacherini, Gianmarco Tosi, Elena De Benedetto, Marco Nardi, Michele Figus, Chiara Posarelli, Cesare Mariotti, Vittorio Pirani, Michele Nicolai, Stefano Bonini, Marco Coassin, Antonio Di Zazzo, Mariacristina Savastano, Alfonso Savastano, Gloria Gambini, Umberto De Vico, Leopoldo Spadea, Andrea Iannaccone, Carlo Nucci, Federico Ricci, Francesco Aiello, Gabriele Gallo Afflitto, Leonardo Mastropasqua, Giada D’Onofio, Federica Evangelista, Lorenza Brescia, Pasquale Napolitano, Paolo Polisena, Nicolina Gianfrancesco, Domenico Trivisonno, Francesco Petti, Francesca Simonelli, Settimio Rossi, Antonio Tartaglione, Nicola Rosa, Maddalena De Bernardo, Cristiana Iaculli, Anna Valeria Bux, Giulia Maggiore, Francesco Boscia, Giancarlo Sborgia, Maria Oliva Grassi, Vincenzo Scorcia, Giuseppe Giannaccare, Guglielmo Parisi, Salvatore Cillino, Francesco Alaimo, Pasquale Aragona, Alessandro Meduri, Antonio Pinna, Andrea Sollazzo, Enrico Peiretti, Emanuele Siotto, dell’Omo, Roberto, Filippelli, Mariaelena, Virgili, Gianni, Bandello, Francesco, Querques, Giuseppe, Lanzetta, Paolo, Avitabile, Teresio, Viola, Francesco, Reibaldi, Michele, Semeraro, Francesco, Quaranta, Luciano, Rizzo, Stanislao, Midena, Edoardo, Campagna, Giuseppe, Costagliola, Ciro, Marolo, Paola, Traverso, Carlo Enrico, Iester, Michele, Cutolo, Carlo Alberto, Azzolini, Claudio, Donati, Simone, Premi, Elia, Nucci, Paolo, Vujosevic, Stela, Staurenghi, Giovanni, Bottoni, Ferdinando, Romano, Francesco, Grosso, Domenico, Borrelli, Enrico, Sacconi, Riccardo, Milella, Paolo, Ganci, Simone, Romano, Mario R., Ricciardelli, Gabriella, Allegrini, Davide, Casaluci, Marco, Romano, Davide, Marchini, Giorgio, Chemello, Francesca, Amantea, Camilla, Frisina, Rino, Pilotto, Elisabetta, Parrozzani, Raffaele, Veritti, Daniele, Sarao, Valentina, Daniele, Tognetto, Busin, Massimo, Parmeggiani, Francesco, De Nadai, Katia, Furiosi, Luca, Mastropasqua, Rodolfo, Battaglia, Bruno, Gironi, Matteo, Gandolfi, Stefano, Luciani, Enrico, Mora, Paolo, Schiavi, Costantino, Bertaccini, Patrizia, Finzi, Alessandro, Roda, Matilde, Cagini, Carlo, Lupidi, Marco, Giansanti, Fabrizio, Bacherini, Daniela, Tosi, Gianmarco, De Benedetto, Elena, Nardi, Marco, Figus, Michele, Posarelli, Chiara, Mariotti, Cesare, Pirani, Vittorio, Nicolai, Michele, Bonini, Stefano, Coassin, Marco, Di Zazzo, Antonio, Savastano, Mariacristina, Savastano, Alfonso, Gambini, Gloria, Vico, Umberto De, Spadea, Leopoldo, Iannaccone, Andrea, Nucci, Carlo, Ricci, Federico, Aiello, Francesco, Afflitto, Gabriele Gallo, Mastropasqua, Leonardo, D’Onofio, Giada, Evangelista, Federica, Brescia, Lorenza, Napolitano, Pasquale, Polisena, Paolo, Gianfrancesco, Nicolina, Trivisonno, Domenico, Petti, Francesco, Simonelli, Francesca, Rossi, Settimio, Tartaglione, Antonio, Rosa, Nicola, Bernardo, Maddalena De, Iaculli, Cristiana, Valeria Bux, Anna, Maggiore, Giulia, Boscia, Francesco, Sborgia, Giancarlo, Grassi, Maria Oliva, Scorcia, Vincenzo, Giannaccare, Giuseppe, Parisi, Guglielmo, Cillino, Salvatore, Alaimo, Francesco, Aragona, Pasquale, Meduri, Alessandro, Pinna, Antonio, Sollazzo, Andrea, Peiretti, Enrico, Siotto, Emanuele, Dell'Omo, R., Filippelli, M., Virgili, G., Bandello, F., Querques, G., Lanzetta, P., Avitabile, T., Viola, F., Reibaldi, M., Semeraro, F., Quaranta, L., Rizzo, S., Midena, E., Campagna, G., Costagliola, C., Marolo, P., Traverso, C. E., Iester, M., Cutolo, C. A., Azzolini, C., Donati, S., Premi, E., Nucci, P., Vujosevic, S., Staurenghi, G., Bottoni, F., Romano, F., Grosso, D., Borrelli, E., Sacconi, R., Milella, P., Ganci, S., Romano, M. R., Ricciardelli, G., Allegrini, D., Casaluci, M., Romano, D., Marchini, G., Chemello, F., Amantea, C., Frisina, R., Pilotto, E., Parrozzani, R., Veritti, D., Sarao, V., Daniele, T., Busin, M., Parmeggiani, F., De Nadai, K., Furiosi, L., Mastropasqua, R., Battaglia, B., Gironi, M., Gandolfi, S., Luciani, E., Mora, P., Schiavi, C., Bertaccini, P., Finzi, A., Roda, M., Cagini, C., Lupidi, M., Giansanti, F., Bacherini, D., Tosi, G., De Benedetto, E., Nardi, M., Figus, M., Posarelli, C., Mariotti, C., Pirani, V., Nicolai, M., Bonini, S., Coassin, M., Di Zazzo, A., Savastano, M., Savastano, A., Gambini, G., Vico, U. D., Spadea, L., Iannaccone, A., Nucci, C., Ricci, F., Aiello, F., Afflitto, G. G., Mastropasqua, L., D'Onofio, G., Evangelista, F., Brescia, L., Napolitano, P., Polisena, P., Gianfrancesco, N., Trivisonno, D., Petti, F., Simonelli, F., Rossi, S., Tartaglione, A., Rosa, N., Bernardo, M. D., Iaculli, C., Valeria Bux, A., Maggiore, G., Boscia, F., Sborgia, G., Grassi, M. O., Scorcia, V., Giannaccare, G., Parisi, G., Cillino, S., Alaimo, F., Aragona, P., Meduri, A., Pinna, A., Sollazzo, A., Peiretti, E., and Siotto, E.
Subjects: medicine.medical_specialty, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), medicine.medical_treatment, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Trauma, phacoemulsification, glaucoma, retinal detachment, choroidal neovascular membranes, venous occlusive disease, corneal transplantation, Trauma, choroidal neovascular membranes, retinal detachment, Retrospective Studie, Settore MED/30, medicine, Retrospective analysis, choroidal neovascular membrane, Humans, venous occlusive disease, Retrospective Studies, corneal transplantation, glaucoma, phacoemulsification, Communicable Disease Control, SARS-CoV-2, COVID-19, Retinal Detachment, Settore MED/30 - Malattie Apparato Visivo, business.industry, Retinal detachment, General Medicine, Phacoemulsification, Surgical procedures, medicine.disease, Surgery, Ophthalmology, business, trauma, Human
Abstract: Background/objectives: To compare the number of eye surgical procedures performed in Italy in the 2 months following the beginning of lockdown (study period) because of COVID-19 epidemic with those performed in the two earlier months of the same year (intra-year control) and in the period of 2019 corresponding to the lockdown (inter-year control). Methods: Retrospective analysis of surgical procedures carried out at 39 Academic hospitals. A distinction was made between elective and urgent procedures. Intravitreal injections were also considered. Percentages for all surgical procedures and incidence rate ratios (IRR) for rhegmatogenous retinal detachment (RRD) events were calculated. A p value Results: A total of 20,886 versus 55,259 and 56,640 patients underwent surgery during the lockdown versus intra-and inter-year control periods, respectively. During the lockdown, only 70% of patients for whom an operation/intravitreal injection was recommended, finally underwent surgery; the remaining patients did not attend because afraid of getting infected at the hospital (23%), taking public transportation (6.5%), or unavailable swabs (0.5%). Elective surgeries were reduced by 96.2% and 96.4%, urgent surgeries by 49.7% and 50.2%, and intravitreal injections by 48.5% and 48.6% in the lockdown period in comparison to intra-year and inter-year control periods, respectively. IRRs for RRDs during lockdown dropped significantly in comparison with intra- and inter-year control periods (CI: 0.65–0.80 and 0.61–0.75, respectively, p Conclusion: This study provides a quantitative analysis of the reduction of eye surgical procedures performed in Italy because of the COVID-19 epidemic.
Published: 2022

39. Retinal Glial Cells in Von Hippel–Lindau Disease: A Novel Approach in the Pathophysiology of Retinal Hemangioblastoma

Author: Elisabetta Pilotto, Giulia Midena, Tommaso Torresin, Gilda De Mojà, Maria Laura Bacelle, Alfonso Massimiliano Ferrara, Stefania Zovato, and Edoardo Midena
Subjects: Cancer Research, Astrocytes, OCT, Retinal hemangioblastoma, Retinal macroglia, Retinal microglia, Von Hippel–Lindau disease, endocrine system diseases, astrocytes, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, retinal macroglia, urologic and male genital diseases, Article, retinal microglia, female genital diseases and pregnancy complications, Oncology, retinal hemangioblastoma, neoplasms, RC254-282
Abstract: Simple Summary The in vivo optical coherence tomography analysis of the biomarkers of retinal microglia and macroglia in Von Hippel–Lindau disease represents an innovative field of research. The different behavior of these glial cells in Von Hippel–Lindau patients provides new data regarding the pathophysiology of retinal hemangioblastoma, the most common ocular manifestation of this hereditary disorder. Moreover, these biomarkers show a different behavior in Von Hippel–Lindau patients in relation to the presence or absence of retinal hemangioblastoma. Therefore, we can hypothesize that retinal hemangioblastoma is mainly due to the activation of macroglia by previously activated microglial cells. Abstract Background: Von Hippel–Lindau (VHL) disease is a neoplastic syndrome caused by a mutation of the VHL tumor suppressor gene. Retinal hemangioblastoma (RH) is a vascularized tumor and represents the most common ocular manifestation of this disease. At the retinal level, VHL protein is able to regulate tumor growth, angiogenic factors, and neuroinflammation, probably stimulating retinal glial cells. The aim of the present study was to analyze in vivo the optical coherence tomography (OCT) biomarkers of retinal macroglia and microglia in a cohort of VHL patients. Methods: The mean thicknesses of macular retinal nerve fiber layer (mRNFL), ganglion cell layer (GCL), and peripapillary retinal nerve fiber layer (pRNFL) were measured with OCT as biomarkers of retinal macroglia. OCT images were also analyzed to detect and quantify hyperreflective retinal foci (HRF), a biomarker of retinal activated microglia. Results: 61 eyes of 61 VHL patients (22 eyes (36.07%) with peripheral RH and 39 eyes (63.93%) without RH) and 28 eyes of 28 controls were evaluated. pRNFL was thinner in VHL patients (p < 0.05) and in VHL without RH (p < 0.01) compared to controls, and thicker in VHL patients with RH than in those without RH (p < 0.05). The thickness of mRNFL (p < 0.0001) and GCL (p < 0.05) was reduced in VHL patients and in VHL without RH compared to controls, whereas mRNFL (p < 0.0001) and GCL (p < 0.05) were increased in VHL patients with RH compared to those without RH. HRF were significantly higher in number in VHL patients and in VHL without RH, than in controls, and significantly lower (p < 0.05) in the eyes of VHL patients with RH, than in those without RH. Conclusions: The OCT analysis, which detects and allows to quantify the biomarkers of retinal microglia (HRF) and macroglia (pRNFL, mRNFL and GCL), showed a different behavior of these two retinal glial cells populations in VHL patients, related to the presence or absence of peripheral RH. These data allow to hypothesize a novel pathophysiologic pathway of retinal hemangioblastoma in VHL disease.
Published: 2021
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40. Response to comment on 'Intraocular fluid biomarkers (liquid biopsy) in human diabetic retinopathy.' Graefes Arch Clin Exp Ophthalmol. 2021 Jul 3. doi: 10.1007/s00417-021-05285-y

Author: Edoardo Midena, Luisa Frizziero, Elisabetta Pilotto, and Giulia Midena
Subjects: medicine.medical_specialty, Diabetic Retinopathy, business.industry, Liquid Biopsy, Diabetic retinopathy, medicine.disease, Retinal Perforations, Sensory Systems, Aqueous Humor, Cellular and Molecular Neuroscience, Ophthalmology, Intraocular fluid, medicine, Diabetes Mellitus, Humans, Liquid biopsy, business, Biomarkers
Published: 2021

41. Vision-Related Quality of Life in Patients with Diabetic Macular Edema Treated with Intravitreal Aflibercept

Author: Justus G. Garweg, Jana Stefanickova, Carel Hoyng, Thomas Schmelter, Tobias Niesen, Olaf Sowade, Sobha Sivaprasad, Alfredo Adan, Mikulas Alexik, Fareed Ali, Miguel Amaro, Vilma-Jurate Balciuniene, Francesco M. Bandello, Lluis Arias Barquet, Anna Beck, Katharina Bell, Francesco Boscia, Anniken Bures, Ângela Carneiro, David R. Chow, Andrius Cimbalas, Claudia Dahlke, Varma Deepali, John D. Dickinson, Michael Dollin, Chiara Eandi, Karl-Heinz Emmerich, Nicolas Feltgen, João Pereira Figueira, Oliver Findl, Monika Gajdošová, Richard P. Gale, Ivan John Galic, Justus Garweg, Vanessa Gasser-Steiner, Michel Giunta, John R. Gonder, Andrzej Grzybowski, Jan Hamouz, Lars-Olof Hattenbach, Frank G. Holz, Hasan Jesia, Jozef Kaluzny, Agnes Kerenyi, Peter J. Kertes, Frank Koch, Laurent Kodjikan, David E. Lederer, Ivana Liehneova, Katrin Lorenz, Andrew J. Lotery, Martin McKibbin, Geeta V. Menon, Zofia Michalewska, Edoardo Midena, Massimo Nicolo, Andras Papp, Gabriela Pavlovičová, Enrico Peiretti, Sara Vaz-Pereira, Paolo Perri, Ioannis Petropoulos, Frederic Queguiner, Krystyna Raczynska, Laura Sararols-Ramsay, Marek Rękas, Federico Ricci, Bozena Romanowska-Dixon, Helmut G. Sachs, Saddek Mohand-Said, Dirk Sandner, Ursula Schmidt-Erfurth, Walter Sekundo, Andras Seres, Eric Souied, João Castro de Sousa, Andrzej Stankiewicz, Jana Štefaničková, Katarína Struhárová, Jan Studnicka, Enrique Cervera Taulet, Simon Taylor, Slawomir Teper, Attila Vajas, Carlos Cava Valenciano, Balázs Varsányi, Francesco Viola, Gianni Virgili, Lars Wagenfeld, Gavin Walters, Peter Wiedemann, and Tomasz Zarnowski
Subjects: medicine.medical_specialty, Visual acuity, genetic structures, law.invention, 03 medical and health sciences, 0302 clinical medicine, Endophthalmitis, Randomized controlled trial, Quality of life, law, Ophthalmology, Diabetes mellitus, Medicine, Adverse effect, 030304 developmental biology, Aflibercept, 0303 health sciences, business.industry, Diabetic retinopathy, medicine.disease, eye diseases, 030221 ophthalmology & optometry, medicine.symptom, business, medicine.drug
Abstract: Purpose To examine vision-related quality of life in patients with diabetic macular edema (DME) treated with intravitreal aflibercept (EYLEA, Regeneron Pharmaceuticals, Inc, Tarrytown, NY). Design AQUA was a multicenter, open-label, single-arm, phase 4 study. Participants Adults 18 years of age or older with type 1 or 2 diabetes mellitus and DME. Methods Patients received intravitreal aflibercept 2 mg every 8 weeks for 52 weeks, after 5 initial doses every 4 weeks. Main Outcome Measures The primary outcome was the change in 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) total score from baseline to week 52. Secondary outcomes included the change in NEI VFQ-25 near and distant activities subscale scores, best-corrected visual acuity (BCVA; Early Treatment Diabetic Retinopathy Study [ETDRS] letters), and central retinal thickness (CRT) from baseline to week 52. Change in NEI VFQ-25 score at week 52 for better-seeing eyes (BSEs) and worse-seeing eyes (WSEs) also was evaluated. Results A total of 553 patients comprised the full analysis set, and 560 patients comprised the safety analysis set. At baseline, the mean NEI VFQ-25 total score was 70.12, mean BCVA was 61.5 ETDRS letters, and mean CRT was 464.81 μm. A mean of 8.8 injections were administered over 52 weeks. At week 52, the mean improvement from baseline in the NEI VFQ-25 total score was +6.11 (standard deviation [SD], 11.46); the corresponding improvements in near and distant activities were +11.37 (SD, 18.01) and +7.33 (SD, 17.32), respectively. Similarly, improvements in patients whose BSE and WSE were treated were 7.74 (SD, 13.59) and 5.48 (SD, 9.70), respectively. At week 52, mean change in BCVA was +10.0 ETDRS letters (SD, 8.0 ETDRS letters), and mean change in CRT was –175.38 μm (SD, 132.62 μm). Overall, 53.6% of patients reported treatment-emergent adverse events (TEAEs), of whom 26.8% experienced an ocular TEAE in the study eye. The most common serious ocular TEAE was endophthalmitis (0.5% [n = 3]). Five deaths (0.9%) were reported, but were not considered treatment related. Conclusions Intravitreal aflibercept was associated with clinically meaningful improvements in NEI VFQ-25 total score over 52 weeks in patients with DME; these were even more pronounced for near than for distant activities. Adverse events were consistent with the known safety profile of intravitreal aflibercept.
Published: 2019
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42. Safety and tolerability of ranibizumab in uni/bilateral neovascular age-related macular degeneration: 12-month TWEYEs study

Author: Elena Peruzzi, Giovanni Staurenghi, Francesco Bandello, Edoardo Midena, Laura Colombo, Stefania Bassanini, Federico Ricci, Francesco Viola, Tommaso Lupieri Sinibaldi, Bandello, F., Staurenghi, G., Ricci, F., Midena, E., Viola, F., Lupieri Sinibaldi, T., Colombo, L., Peruzzi, E., and Bassanini, S.
Subjects: Male, retina, Visual acuity, genetic structures, Visual Acuity, Angiogenesis Inhibitors, neovascularisation, age-related macular degeneration, bilateral AMD, neovascular age-related macular degeneration, unilateral AMD, vision, Prospective Studies, Prospective cohort study, Aged, 80 and over, Incidence, Incidence (epidemiology), Clinical Science, Middle Aged, Sensory Systems, Choroidal neovascularization, Italy, Tolerability, Intravitreal Injections, Female, medicine.symptom, Tomography, Optical Coherence, medicine.drug, medicine.medical_specialty, Drug-Related Side Effects and Adverse Reactions, Risk Assessment, Drug Administration Schedule, Cellular and Molecular Neuroscience, Ranibizumab, Settore MED/30, Ophthalmology, medicine, Humans, Adverse effect, Aged, business.industry, Macular degeneration, medicine.disease, Choroidal Neovascularization, Wet Macular Degeneration, business
Abstract: BackgroundTo evaluate the safety and tolerability of ranibizumab 0.5 mg in patients with uni/bilateral neovascular age-related macular degeneration (nAMD) and best-corrected visual acuity (BCVA)MethodsIn this 12-month, prospective, multicentre, open-label, single arm, pragmatic interventional study, patients (N=941) aged ≥ 50 years were to receive ranibizumab as per approved label, monthly until maximum stable visual acuity (VA) was achieved (initially, three or more injections may be required). Thereafter, patients were to be monitored monthly for VA and treatment was to be resumed if VA was reduced due to disease activity.ResultsOf the 936 patients treated with ranibizumab at least once during the study, 823/113 were unilaterally/bilaterally (not simultaneously) treated . The mean (SD) number of ranibizumab injections during the study was 5.4 (2.9)/10.6 (5.0) injections in uni/bilaterally treated patients. Three systemic drug-related adverse events (AEs) (all serious, all in unilaterally treated patients) and 18 systemic AE of special interest (AESIs) (11 serious, 16/2 in unilaterally/bilaterally treated patients) occurred during the study. The annual incidence rate (AIR) (events/1000 person-years) for systemic drug-related AEs, considering a 15-day/30-day risk period, 11.0/8.5 for unilaterally treated patients. Considering the same risk period, the AIR (events/1000 person-years) for systemic AESIs for unilaterally treated patients was 22.1/19.9. Considering a 30-day risk period, the AIR (events/1000 treated eye-years) of ocular drug-related AEs was 23 and AESIs was 11.5.ConclusionsThe low incidence of AEs and AESIs demonstrated the good safety and tolerability of ranibizumab in unilaterally/bilaterally treated patients with nAMD in this real-world setting.
Published: 2019
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43. Increased High-Density Lipoprotein Levels Associated with Age-Related Macular Degeneration

Author: Johanna M. Colijn, Anneke I. den Hollander, Ayse Demirkan, Audrey Cougnard-Grégoire, Timo Verzijden, Eveline Kersten, Magda A. Meester-Smoor, Benedicte M.J. Merle, Grigorios Papageorgiou, Shahzad Ahmad, Monique T. Mulder, Miguel Angelo Costa, Pascale Benlian, Geir Bertelsen, Alain M. Bron, Birte Claes, Catherine Creuzot-Garcher, Maja Gran Erke, Sascha Fauser, Paul J. Foster, Christopher J. Hammond, Hans-Werner Hense, Carel B. Hoyng, Anthony P. Khawaja, Jean-Francois Korobelnik, Stefano Piermarocchi, Tatiana Segato, Rufino Silva, Eric H. Souied, Katie M. Williams, Cornelia M. van Duijn, Cécile Delcourt, Caroline C.W. Klaver, Niyazi Acar, Lebriz Altay, Eleftherios Anastosopoulos, Augusto Azuara-Blanco, Tos Berendschot, Arthur Bergen, Christine Binquet, Alan Bird, Martin Bobak, Morten Bøgelund Larsen, Camiel Boon, Rupert Bourne, Lionel Brétillon, Rebecca Broe, Alain Bron, Gabrielle Buitendijk, Maria Luz Cachulo, Vittorio Capuano, Isabelle Carrière, Usha Chakravarthy, Michelle Chan, Petrus Chang, Johanna Colijn, Angela Cree, Phillippa Cumberland, José Cunha-Vaz, Vincent Daien, Eiko De Jong, Gabor Deak, Marie-Noëlle Delyfer, Anneke den Hollander, Martha Dietzel, Pedro Faria, Claudia Farinha, Robert Finger, Astrid Fletcher, Paul Foster, Panayiota Founti, Theo Gorgels, Jakob Grauslund, Franz Grus, Christopher Hammond, Thomas Heesterbeek, Manuel Hermann, René Hoehn, Ruth Hogg, Frank Holz, Carel Hoyng, Nomdo Jansonius, Sarah Janssen, Eiko de Jong, Anthony Khawaja, Caroline Klaver, Jean-François Korobelnik, Julia Lamparter, Mélanie Le Goff, Terho Lehtimäki, Irene Leung, Andrew Lotery, Matthias Mauschitz, Magda Meester, Bénédicte Merle, Verena Meyer zu Westrup, Edoardo Midena, Stefania Miotto, Alireza Mirshahi, Sadek Mohan-Saïd, Michael Mueller, Alyson Muldrew, Joaquim Murta, Stefan Nickels, Sandrina Nunes, Christopher Owen, Tunde Peto, Norbert Pfeiffer, Elena Prokofyeva, Jugnoo Rahi, Olli Raitakari, Franziska Rauscher, Luisa Ribeiro, Marie-Bénédicte Rougier, Alicja Rudnicka, José Sahel, Aggeliki Salonikiou, Clarisa Sanchez, Tina Schick, Steffen Schmitz-Valckenberg, Alexander Schuster, Cédric Schweitzer, Jasmin Shehata, Giuliana Silvestri, Christian Simader, Eric Souied, Martynas Speckauskas, Henriet Springelkamp, Robyn Tapp, Fotis Topouzis, Elisa van Leeuwen, Virginie Verhoeven, Hans Vingerling, Therese Von Hanno, Katie Williams, Christian Wolfram, Jennifer Yip, Jennyfer Zerbib, Soufiane Ajana, Blanca Arango-Gonzalez, Verena Arndt, Vaibhav Bhatia, Shomi S. Bhattacharya, Marc Biarnés, Anna Borrell, Sebastian Bühren, Sofia M. Calado, Sascha Dammeier, Eiko K. de Jong, Berta De la Cerda, Francisco J. Diaz-Corrales, Sigrid Diether, Eszter Emri, Tanja Endermann, Lucia L. Ferraro, Míriam Garcia, Thomas J. Heesterbeek, Sabina Honisch, Ellen Kilger, Hanno Langen, Imre Lengyel, Phil Luthert, Cyrille Maugeais, Magda Meester-Smoor, Bénédicte M.J. Merle Inserm, Jordi Monés, Everson Nogoceke, Frances M. Pool, Eduardo Rodríguez, Marius Ueffing, Karl U. Ulrich Bartz-Schmidt, Elisabeth M. van Leeuwen, and Markus Zumbansen
Subjects: genetic structures, Blood lipids, Physiology, Drusen, 03 medical and health sciences, Rotterdam Study, 0302 clinical medicine, Cholesterylester transfer protein, medicine, media_common.cataloged_instance, European union, 030304 developmental biology, media_common, 2. Zero hunger, 0303 health sciences, biology, business.industry, Lipid metabolism, Odds ratio, Macular degeneration, medicine.disease, eye diseases, 3. Good health, Ophthalmology, 030221 ophthalmology & optometry, biology.protein, lipids (amino acids, peptides, and proteins), sense organs, business
Abstract: PURPOSE: Genetic and epidemiologic studies have shown that lipid genes and High Density Lipoproteins (HDL) are implicated in age-related macular degeneration (AMD). We studied circulating lipid levels in relation to AMD in a large European dataset, and investigated whether this relationship is driven by certain sub fractions. DESIGN: (Pooled) analysis of cross-sectional data. PARTICIPANTS: 30,953 individuals aged 50+ participating in the E3 consortium; and 1530 individuals from the Rotterdam Study with lipid sub fraction data. METHODS: In E3, AMD features were graded per eye on fundus photographs using the Rotterdam Classification. Routine blood lipid measurements were available from each participant. Data on genetics, medication and confounders such as body mass index, were obtained from a common database. In a subgroup of the Rotterdam Study, lipid sub fractions were identified by the Nightingale biomarker platform. Random-intercepts mixed-effects models incorporating confounders and study site as a random-effect were used to estimate the associations. MAIN OUTCOME MEASURES: early, late or any AMD, phenotypic features of early AMD, lipid measurements. RESULTS: HDL was associated with an increased risk of AMD, corrected for potential confounders (Odds Ratio (OR) 1.21 per 1mmol/L increase (95% confidence interval[CI] 1.14-1.29); while triglycerides were associated with a decreased risk (OR 0.94 per 1mmol/L increase [95%CI 0.91-0.97]). Both were associated with drusen size, higher HDL raises the odds of larger drusen while higher triglycerides decreases the odds. LDL-cholesterol only reached statistical significance in the association with early AMD (p=0.045). Regarding lipid sub fractions: the concentration of extra-large HDL particles showed the most prominent association with AMD (OR 1.24 [95%CI 1.10-1.40]). The CETP risk variant (rs17231506) for AMD was in line with increased-HDL levels (p=7.7x10-7); but LIPC risk variants (rs2043085, rs2070895) were associated in an opposite way (p=1.0x10-6 and 1.6x10-4). CONCLUSIONS: Our study suggests that HDL-cholesterol is associated with increased risk of AMD and triglycerides negatively associated. Both show the strongest association with early AMD and drusen. Extra-large HDL sub fractions seem to be drivers in the relation with AMD, variants in lipid genes play a more ambiguous role in this association. Whether systemic lipids directly influence AMD or represent lipid metabolism in the retina remains a question to be answered.
Published: 2019
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44. Two novel compound heterozygous

Author: Elisabetta, Pilotto, Eva, Trevisson, Elisabetta Beatrice, Nacci, Evelyn, Longhin, Francesca, Guidolin, and Edoardo, Midena
Subjects: G-Protein-Coupled Receptor Kinase 1, Night Blindness, Mutation, Electroretinography, Vision Disorders, Humans, Eye Diseases, Hereditary, Female, Middle Aged
Abstract: Oguchi disease is a rare autosomal recessive retinal dystrophy, characterized by congenital stationary blindness and caused by pathogenic variants inA 60-year-old female complaining congenital stationary night blindness was investigated through fundus photograph, optical coherence tomography (OCT), electroretinography (ERG), and genetic testing.Fundus examination showed a golden-grayish fundus aspect. The rod response of the scotopic ERG was undetectable and mixed rod-cone response was electronegative. Fundus photographs obtained in light and in prolonged dark-adapted conditions allowed to detect the Mizuo-Nakamura phenomenon. Light condition OCT over the abnormal retinal regions showed high-intensity areas in the outer photoreceptor segment layer, that reduced with prolonged dark adaption. Genetic testing identified two rare heterozygous sequence variants in theWe identified the first Italian compound heterozygous patient harboring two novel alterations in the
Published: 2021

45. Diabetic Macular Edema Treated with 577-nm Subthreshold Micropulse Laser: A Real-Life, Long-Term Study

Author: Raffaele Parrozzani, Andrea Calciati, Giulia Midena, Luisa Frizziero, Elisabetta Pilotto, Tommaso Torresin, and Edoardo Midena
Subjects: medicine.medical_specialty, Visual acuity, genetic structures, Diabetic macular edema, Medicine (miscellaneous), subthreshold micropulse laser, 030209 endocrinology & metabolism, autofluorescence, Article, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Optical coherence tomography, Ophthalmology, Statistical significance, medicine, real-life, Adverse effect, optical coherence tomography, medicine.diagnostic_test, Subthreshold conduction, business.industry, 577-nm laser, diabetic macular edema, diabetic retinopathy, laser fixed parameters, Retinal, Diabetic retinopathy, medicine.disease, eye diseases, chemistry, 030221 ophthalmology & optometry, Medicine, medicine.symptom, business
Abstract: The aim of this study was to evaluate the long-term efficacy and safety of 577-nm subthreshold micropulse laser (SMPL) treatment in a large population of patients affected by mild diabetic macular edema (DME) in a real-life setting. We retrospectively evaluated 134 eyes affected by previously untreated center-involving mild DME, and treated with 577-nm SMPL, using fixed parameters. Retreatment was performed at 3 months, in case of persistent retinal thickening. Optical coherence tomography (OCT), along with short and near-infrared fundus autofluorescence, were used to confirm long-term safety. At the end of at least one year follow-up, a significant improvement in visual acuity was documented, compared to baseline (77.3 ± 4.5 and 79.4 ± 4.4 ETDRS score at baseline and at final follow-up, respectively), as well as a reduction in the mean retinal thickness of the thickest ETDRS macular sector at baseline. A reduction in the central retinal thickness and the mean thickness of the nine ETDRS sectors was also found, without reaching statistical significance. No patients required intravitreal injections. No adverse effects were detected. This study suggests that 577-nm SMPL is a safe and repeatable treatment for mild DME that may be applied to real-life clinical settings using fixed parameters and protocols.
Published: 2021

46. Reper intraocular lens with artificial iris: implantation techniques and outcomes

Author: Rino Frisina, Edoardo Midena, Catia Gambato, Chiara Sofia De Biasi, Davide Londei, Irene Gius, and Luigi Tozzi
Subjects: medicine.medical_specialty, genetic structures, medicine.medical_treatment, Visual Acuity, Iris, Intraocular lens, Aphakia, Prosthesis, 03 medical and health sciences, 0302 clinical medicine, Suture (anatomy), Lens Implantation, Intraocular, Medicine, Humans, Aniridia, aphakia, artificial iris, corneal transplantation, ocular reconstruction, trauma, Corneal transplantation, Lenses, Intraocular, business.industry, Suture Techniques, General Medicine, medicine.disease, eye diseases, Surgery, Ophthalmology, medicine.anatomical_structure, Lens (anatomy), 030221 ophthalmology & optometry, sense organs, Implant, business, 030217 neurology & neurosurgery
Abstract: The authors describe the surgical techniques to implant a novel intraocular lens with artificial iris (Reper) in patients affected by traumatic aphakia and aniridia. Two surgical approaches are proposed: implantation by suture-loaded cartridge and “open sky” implantation combined with penetrating keratoplasty. The method of establishing the exact position of the scleral fixation points and the pre-assembly of the suture of Reper before its implantation are the main novel proposed surgical procedures. The rationale is to minimize surgical procedures in the anterior chamber and to prevent knot loosening and lens tilting. The simultaneous treatment of aphakia and aniridia with a single prosthesis, the stability of the Reper and the functional, anatomical and aesthetic outcomes obtained are the highlighted advantages in this study.
Published: 2021

47. Real-life patient journey in neovascular age-related macular degeneration: a narrative medicine analysis in the Italian setting

Author: Maria Giulia Marini, Edoardo Midena, Luisa Frizziero, Simone Donati, Monica Camparini, Monica Varano, Maurizio Battaglia Parodi, Luigi Reale, Maria Vadalà, Giovanni Staurenghi, Elisabetta Pilotto, Alfredo Pece, Alessandra Fiorencis, Midena E., Varano M., Pilotto E., Staurenghi G., Camparini M., Pece A., Battaglia Parodi M., Vadalà Maria, Donati S., Frizziero L., Fiorencis A., Marini M.G., Reale L., Midena E, Varano M, Pilotto E, Staurenghi G, Camparini M, Pece A, Battaglia Parodi M, Vadala' M, Donati S, Frizziero L, Fiorencis A, Marini MG, Reale L., Midena, E., Varano, M., Pilotto, E., Staurenghi, G., Camparini, M., Pece, A., Battaglia Parodi, M., Vadala, M., Donati, S., Frizziero, L., Fiorencis, A., Marini, M. G., and Reale, L.
Subjects: Vascular Endothelial Growth Factor A, medicine.medical_specialty, Activities of daily living, age related macular degeneration, MEDLINE, Angiogenesis Inhibitors, Disease, Article, 03 medical and health sciences, Macular Degeneration, 0302 clinical medicine, Multidisciplinary approach, Ranibizumab, Health care, real life, Medicine, patient journey, Humans, Narrative, education, Narrative medicine, education.field_of_study, Narrative medicine, wet AMD, business.industry, Settore MED/30 - Malattie Apparato Visivo, Narrative Medicine, Macular degeneration, medicine.disease, Ophthalmology, Family medicine, Intravitreal Injections, 030221 ophthalmology & optometry, Quality of Life, Wet Macular Degeneration, business, 030217 neurology & neurosurgery
Abstract: Objectives To investigate the real-life experience of patients affected by neovascular age-related macular degeneration (nAMD), in the healthcare pathway for the management of the disease, using a "patient journey" and narrative method approach. Methods The patient journey of subjects affected by nAMD was designed using a process-mapping methodology involving a team from 11 Italian centres. Subsequently, narratives were collected from nAMD patients and family members. The interviews were analyzed using the narrative medicine methodology. Results Eleven specialized retina centres across Italy were involved and 205 narratives collected. In 29% of cases, patients underestimated their symptoms or attributed them to non-pathological causes, thus delaying the specialist consultation. The delay in accessing to care was due to a lack of awareness of this disease (50% of the participants didn't know what nAMD is) and to critical issues faced at first visit (long waiting lists, failed diagnosis, underestimation of the problem). Despite anti-VEGF therapies were perceived as effective in improving or stabilizing vision in 91% of narratives collected, 77% of patients still reduced or ceased daily activities such as reading and driving. Within the pathway of care there was not a multidisciplinary approach, and the patients were treated just by the ophthalmologist. Conclusions nAMD may significantly affect the quality of life of affected patients, both from a functional and psychological point of view. The narrative medicine approach highlights some critical points in the healthcare journey of nAMD patients and represents a useful background in implementing patient management algorithms and pathways of care.
Published: 2021

48. Refractory full thickness macular hole: current surgical management

Author: Luigi Tozzi, Rino Frisina, Irene Gius, and Edoardo Midena
Subjects: Pars plana, medicine.medical_specialty, Visual acuity, genetic structures, medicine.medical_treatment, Vitrectomy, Review Article, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Refractory, Ophthalmology, Full-thickness macular hole, Medicine, Macular hole, business.industry, Retinal, medicine.disease, eye diseases, Transplantation, medicine.anatomical_structure, chemistry, 030221 ophthalmology & optometry, sense organs, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: This review aims to collect the proposed surgical techniques for treating full thickness macular hole (FTMH) refractory to pars plana vitrectomy and internal limiting membrane (ILM) peeling and to analyse and compare anatomical and functional outcomes in order to evaluate their efficacy. The articles were grouped according to the surgical techniques used. Refractory FTMH closure rate and best-corrected visual acuity (BCVA) gain were the two analysed parameters. Thirty-six articles were selected. Ten surgical technique subgroups were defined: autologous platelet concentrate (APC); lens capsular flap transplantation (LCFT); autologous free ILM flap transplantation (free ILM flap); enlargement of ILM peeling, macular hole hydrodissection (MHH), autologous retinal graft (ARG), silicon oil (SO), human amniotic membrane (hAM), perifoveal relaxing retinotomy, arcuate temporal retinotomy. Refractory FTMH closure rate was similar among subgroups, not significant heterogeneity emerged (p = 0.176). BCVA gain showed a significant dependence on surgical technique (p
Published: 2021

49. Early microvascular and oscillatory potentials changes in human diabetic retina: Amacrine cells and the intraretinal neurovascular crosstalk

Author: Evelyn Longhin, Giulia Midena, Tommaso Torresin, Elisabetta Pilotto, Luisa Frizziero, and Edoardo Midena
Subjects: medicine.medical_specialty, Oscillatory potentials, Vascular plexuses, Article, chemistry.chemical_compound, Amacrine cells, Optical coherence tomography, Diabetic retinopathy, Ophthalmology, medicine, Electroretinography, Intraretinal crosstalk, Morpho-functional correlations, Optical coherence tomography angiography, Oscillatory poten-tials, medicine.diagnostic_test, business.industry, Retinal, General Medicine, medicine.disease, Neurovascular bundle, Pathophysiology, oscillatory potentials, Crosstalk (biology), chemistry, Medicine, business
Abstract: To analyze the early microvascular retinal changes and oscillatory potentials alterations secondary to diabetic retinal damage, 44 eyes of 22 diabetic patients without and with mild diabetic retinopathy (DR) and 18 eyes of 9 healthy controls were examined. All subjects underwent spectral domain optical coherence tomography (SD-OCT), OCT angiography (OCTA), and electroretinography of oscillatory potentials (OPs). At OCTA, vessel area density (VAD), vessel length fraction (VLF), and fractal dimension (FD) were significantly reduced in the superficial vascular plexus (SVP), VLF and FD in the intermediate capillary plexus (ICP), and FD in the deep capillary plexus (DCP) in the diabetic group compared to the control group. The amplitude (A) of OP2, OP3, OP4 and the sum of OPs were significantly reduced in the diabetic group versus the controls, and the last two parameters were reduced also in patients without DR versus the controls. Moreover, in the diabetic group, a significant direct correlation was found between the A of OP1, OP2, OP3 and sOP and the VLF and FD in the SVP, while a statistically significant inverse correlation was found between the A of OP3 and OP4 and the VDI in the ICP and DCP. The reduced oscillatory potentials suggest a precocious involvement of amacrine cells in diabetic eyes, independently of DR presence, and their correlation with vascular parameters underlines the relevance of the crosstalk between these cells and vascular components in the pathophysiology of this chronic disease.
Published: 2021

50. Structural and microvascular changes of the peripapillary retinal nerve fiber layer in Von Hippel–Lindau disease: an OCT and OCT angiography study

Author: Gilda De Mojà, Elisabetta Pilotto, Davide Londei, Raffaele Parrozzani, Elisabetta Beatrice Nacci, Stefania Zovato, Alfonso Massimiliano Ferrara, and Edoardo Midena
Subjects: 0301 basic medicine, Male, von Hippel-Lindau Disease, genetic structures, Nerve fiber layer, urologic and male genital diseases, chemistry.chemical_compound, 0302 clinical medicine, Nerve Fibers, education.field_of_study, Multidisciplinary, medicine.diagnostic_test, Microvascular Density, Angiography, Middle Aged, Hemangioblastoma, medicine.anatomical_structure, Medicine, Female, medicine.symptom, VHL Gene Mutation, Perfusion, Tomography, Optical Coherence, Adult, medicine.medical_specialty, Science, Retinal Neoplasms, Population, Predictive markers, Article, Lesion, Cancer screening, 03 medical and health sciences, Ophthalmology, medicine, Humans, education, business.industry, Retinal Vessels, Retinal, eye diseases, 030104 developmental biology, Cross-Sectional Studies, chemistry, Case-Control Studies, Microvessels, 030221 ophthalmology & optometry, sense organs, business
Abstract: Von Hippel–Lindau (VHL) disease is an autosomal dominant genetic disease caused by VHL gene mutation. Retinal hemangioblastomas (RH) are vascularized tumors and represent the main ocular manifestation of the disease. Histopathologically, RH are composed of capillary vessels and stromal cells, the neoplastic population of the lesion. The origin of these stromal cells remains controversial, even if they are hypothesized to be glial cells. The aim of the present study was to investigate neuronal and microvascular changes of the peripapillary retinal nerve fiber layer, in which glial cells, neurons and capillaries (the radial peripapillary capillary plexus) interact. VHL patients with or without peripheral RH were enrolled and compared to healthy controls. Mean peripapillary retinal nerve fiber layer (pRNFL) thickness was measured by means of optical coherence tomography (OCT). The following vascular parameters of the radial peripapillary capillary plexus were quantified using OCT angiography: Vessel Area Density,Vessel Length Fraction, Vessel Diameter Index and Fractal Dimension. One hundred and nine eyes of 61 patients, and 56 eyes of 28 controls were consecutively studied. Mean pRNFL was significantly thinner in VHL eyes without RH versus eyes with RH and controls. Mean pRNFL thickness did not differ between VHL eyes with RH and controls. All OCTA vascular parameters were reduced in VHL eyes with or without RH versus controls, with significative difference for Vessel Diameter Index. The same OCTA parameters did not significantly differ between VHL eyes with or without RH. In VHL eyes without RH, pRNFL thinning may be the consequence of impaired perfusion of the radial peripapillary capillary plexus, while the increase of pRNFL thickness in VHL eyes with RH may depend on possible activation and proliferation of the other RNFL resident cells, the glial cells.
Published: 2021

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