Intravitreal Aflibercept vs Laser Therapy for Retinopathy of Prematurity: Two-Year Efficacy and Safety Outcomes in the Nonrandomized Controlled Trial FIREFLEYE next.

Abstract

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.

• 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, FIREFLEYE next Study Group
• Journal: JAMA network open (JAMA Netw Open) Vol. 7 Issue 4 Pg. e248383 (Apr 01 2024) ISSN: 2574-3805 [Electronic] United States
• PMID: 38687481 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Randomized Controlled Trial, Multicenter Study, Comparative Study)

Chemical References

• Receptors, Vascular Endothelial Growth Factor
• Recombinant Fusion Proteins
• aflibercept
• Angiogenesis Inhibitors

Topics

• Humans
• Retinopathy of Prematurity (surgery, therapy, drug therapy)
• Receptors, Vascular Endothelial Growth Factor (therapeutic use)
• Recombinant Fusion Proteins (therapeutic use, adverse effects, administration & dosage)
• Intravitreal Injections
• Female
• Male
• Infant, Newborn
• Prospective Studies
• Treatment Outcome
• Angiogenesis Inhibitors (therapeutic use, adverse effects)
• Laser Therapy (methods, adverse effects)
• Infant
• Child, Preschool