Intravitreal Aflibercept vs Laser Therapy for Retinopathy of Prematurity
Authors: Andreas Stahl, Hidehiko Nakanishi, Domenico Lepore, Wei-Chi Wu, Noriyuki Azuma, Carlos Jacas, Robert Vitti, Aditya Athanikar, Karen Chu, Pablo Iveli, Fei Zhao, Sergio Leal, Sarah Schlief, Thomas Schmelter, Thomas Miller, Evra Köfüncü, Alistair Fielder, Pablo Larrea, Patricia Delbeke, Nilva de Moraes, Maria Regina Bentlin, Violeta Chernodrinska, Christina Grupcheva, Liliyana Dimitrova, Vasil Marinov, Magdalena Kovacova, Juraj Timkovic, Ioannis Asproudis, Agathi Kouri, Asimina Mataftsi, Erzsebet Princzkel, Hana Leiba, Luca Buzzonetti, Carlo Cagini, Domenico Lepore, Silvia Gabriella Osnaghi, Mitsuru Arima, Hideyuki Hayashi, Mariko Kiyota, Hiroyuki Kondo, Shunji Kusaka, Tomoko Miyazato, Eiichiro Noda, Yasunobu Saneyoshi, Tetsuju Sekiryu, Takako Tachikawa, Nor Akmal Bahari, Stefan de Geus, Frank Kerkhoff, Ana Almeida, Susana Teixeira, Narcis Berlea, Delia Nicoara, Yulia Gorelik, Eyvgeny Sidorenko, Irina Trifanenkova, Bin Huey Quek, Dana Tomcikova, So Young Kim, Joo Yong Lee, Jesús Peralta Calvo, Julia Escudero Gómez, Pilar Tejada Palacios, Ann Hellström, Yu-Hung Lai, Hsiang-Ling Tsai, Hikmet Basmak, Sibel Caliskan Kadayifcilar, Muhammet Erol, Sengul Ozdek, Hatice Tugba Atalay, Zeynep Canserver, Emine Sukgen, Sally Painter, Sergii Katsan
Journal: JAMA Network Open (2024)

Importance Prospective long-term data after retinopathy of prematurity (ROP) treatment with anti–vascular endothelial growth factor injections vs laser therapy are scarce. The FIREFLEYE (Aflibercept for ROP IVT Injection vs Laser Therapy) next trial is prospectively evaluating the long-term efficacy and safety outcomes following ROP treatment with intravitreal aflibercept vs laser therapy. Objective To evaluate 2-year ophthalmic and safety outcomes after 0.4-mg aflibercept injection or laser therapy in the 24-week randomized (2:1) FIREFLEYE trial (FIREFLEYE outcomes previously reported). Design, Setting, and Participants This prospective nonrandomized controlled trial performed in 24 countries in Asia, Europe, and South America (2020-2025) follows up participants treated in the FIREFLEYE randomized clinical trial (2019-2021) through 5 years of age. Participants included children born very or extremely preterm (gestational age ≤32 weeks) or with very or extremely low birth weight (≤1500 g) who were previously treated with a 0.4-mg injection of aflibercept compared with laser therapy for severe acute-phase ROP. Data for the present interim analysis were acquired from March 18, 2020, to July 25, 2022. Interventions Complications of ROP treated at investigator discretion (no study treatment). Main Outcomes and Measures Efficacy end points included ROP status, unfavorable structural outcomes, ROP recurrence, treatment for ROP complications, completion of vascularization, and visual function. Safety end points included adverse events and growth and neurodevelopmental outcomes. Results Overall, 100 children were enrolled (median gestational age, 26 [range, 23-31] weeks; 53 boys and 47 girls). Of these, 21 were Asian, 2 were Black, 75 were White, and 2 were of more than 1 race. At 2 years of age, 61 of 63 children (96.8%) in the aflibercept group vs 30 of 32 (93.8%) in the laser group had no ROP. Through 2 years of age, 62 of 66 (93.9%) in the aflibercept group and 32 of 34 (94.1%) in the laser group had no unfavorable structural outcomes. No new retinal detachment occurred during the study. Four children in the aflibercept group (6.1%) were treated for ROP complications before 1 year of age (2 had preexisting end-stage disease and total retinal detachment; 1 had reactivated plus disease; and 1 had recurrent retinal neovascularization not further specified). Most children were able to fix and follow a 5-cm toy (aflibercept group, 118 of 122 eyes [96.7%] among 63 children; laser group, 62 of 63 eyes [98.4%] among 33 children). High myopia was present in 9 of 115 eyes (7.8%) among 5 children in the aflibercept group and 13 of 60 eyes (21.7%) among 9 children in the laser group. No relevant differences in growth and neurodevelopmental outcomes by Bayley Scales of Infant and Toddler Development, Third Edition and Vineland Adaptive Behavior Scales, Second Edition were identified. Conclusions and Relevance In this nonrandomized follow-up of a randomized clinical trial comparing treatment of severe acute-phase ROP with 0.4-mg injection of aflibercept and laser, disease control was stable and visual function was appropriate in children through 2 years of age. No adverse effects on safety, including growth and neurodevelopment, were identified. These findings provide clinically relevant long-term information on intravitreal aflibercept injection therapy for ROP. Trial Registration ClinicalTrials.gov Identifier: NCT04015180