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