Ranibizumab versus laser therapy for the treatment of very low birthweight infants with retinopathy of prematurity (RAINBOW): five-year outcomes of a randomised trial

Neil Marlow; James D Reynolds; Domenico Lepore; Alistair R Fielder; Andreas Stahl; Han Hao; Annemarie Weisberger; Amit Lodha; Brian W Fleck

doi:10.1016/j.eclinm.2024.102567

Ranibizumab versus laser therapy for the treatment of very low birthweight infants with retinopathy of prematurity (RAINBOW): five-year outcomes of a randomised trial

EClinicalMedicine. 2024 Apr 11:71:102567. doi: 10.1016/j.eclinm.2024.102567. eCollection 2024 May.

Authors

Neil Marlow¹, James D Reynolds², Domenico Lepore³, Alistair R Fielder⁴, Andreas Stahl⁵, Han Hao⁶, Annemarie Weisberger⁷, Amit Lodha⁸, Brian W Fleck⁹

Affiliations

¹ UCL Elizabeth Garrett Anderson Institute for Women's Health, University College London, London, UK.
² Ross Eye Institute, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, USA.
³ Department of Neuroscience, Sensory Organs and Thorax, Catholic University of the Sacred Heart, Gemelli Foundation IRCSS, Rome, Italy.
⁴ Department of Optometry & Visual Science, City, University of London, UK.
⁵ Department of Ophthalmology, University Medical Center Greifswald, Germany.
⁶ China Novartis Institutes for BioMedical Research Company Ltd.
⁷ Novartis Pharma AG, Basel, Switzerland.
⁸ Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
⁹ Centre for Clinical Brain Sciences, University of Edinburgh, UK.

Abstract

Background: Concerns remain over the long-term safety of vascular endothelial growth factor (VEGF) inhibitors to treat retinopathy of prematurity (ROP). RAINBOW is an open label randomised trial comparing intravitreal ranibizumab (in 0.2 mg and 0.1 mg doses) with laser therapy in very low birthweight infants (<1500 g) with ROP.

Methods: Of 201 infants completing RAINBOW, 180 were enrolled in the RAINBOW Extension Study. At 5 years, children underwent ophthalmic, development and health assessments. The primary outcome was visual acuity in the better-seeing eye. The study is registered with ClinicalTrial.gov, NCT02640664.

Findings: Between 16-6-2016 and 21-4-2022, 156 children (87%) were evaluated at 5 years. Of 32 children with no acuity test result, 25 had a preferential looking test, for 4 children investigators reported low vision for each eye, and in 3 further children no vision measurement was obtained. 124 children completed the acuity assessment, the least square mean (95% CI) letter score in the better seeing eye was similar in the three trial arms-66.8 (62.9-70.7) following ranibizumab 0.2 mg, 64.6 (60.6-68.5) following ranibizumab 0.1 mg and 62.1 (57.8-66.4) following laser therapy; differences in means: ranibizumab 0.2 mg v laser: 4.7 (95% CI: -1.1, 10.5); 0.1 mg v laser: 2.5 (-3.4, 8.3); 0.2 mg v 0.1 mg: 2.2 (-3.3, 7.8). High myopia (worse than -5 dioptres) in at least one eye occurred in 4/52 (8%) children following ranibizumab 0.2 mg, 8/55 (15%) following ranibizumab 0.1 mg and 11/45 (24%) following laser therapy (0.2 mg versus laser: odds ratio: 3.99 (1.16-13.72)). Ocular and systemic secondary outcomes and adverse events were distributed similarly in each trial arm.

Interpretation: 5-year outcomes confirm the findings of the original RAINBOW trial and a planned interim analysis at 2 years, including a reduced frequency of high myopia following ranibizumab treatment. No effects of treatment on non-ocular outcomes were detected.

Funding: Novartis Pharma AG.

Keywords: Anti-VEGF treatment; Infant; Neurodevelopment; Preterm; Randomised controlled trial; Retinopathy of prematurity.

Associated data

ClinicalTrials.gov/NCT02640664