OSLI Retina

October 2020

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542 Ophthalmic Surgery, Lasers & Imaging Retina | Healio.com/OSLIRetina ■ E D I T O R I A L ■ Playing With Fire C. Armitage Harper III, MD; Kinley D. Beck, MD; Emmanuel Chang, MD, PhD; Ryan Young, MD; Darius M. Moshfeghi, MD ABSTRACT: The authors present their concerns surrounding data presented in studies from 2018 and 2020 regarding very low dose bevacizumab for the treatment of retinopathy of prematurity. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:542-544.] We appreciate the collaborative effort and ini- tiative of Wallace et al. 1,2 to investigate the lowest effective dose of intravitreal bevacizumab (IVB) (Avastin; Genentech, South San Francisco, CA) for the treatment of type 1 retinopathy of prematuri- ty (ROP). Given the biological plausibility of sys- temic effects from IVB, dose de-escalation studies are important to establish the safety and efficacy of its use in the treatment of ROP. These studies and the authors' conclusion that retinal structural outcomes are "very good" with low doses of IVB have brought several concerns to our attention that should be addressed. First, the above premise of us- ing low-dose IVB is predicated upon the theoretical conclusion that higher-dose IVB results in lower serum levels of vascular endothelial growth factor (VEGF) with subsequent systemic complications. Were serum VEGF levels measured? If so, were the measurements proportional to IVB dose? If not, this lack of data seems to obviate the hypothesis of the study. In addition, recent evidence from the RAIN- BOW trial indicates that there were no differences in the plasma-free concentrations of VEGF between the ranibizumab 0.1 mg group, ranibizumab 0.2 mg group, or laser group over time. 3 Given this infor- mation and the aforementioned limitations, intra- vitreal ranibizumab (IVR) would be theoretically safer based on molecular structure, and lowering the dose would not be necessary. In the 2018 de-escalation study, 25 of the 61 study eyes (41%) required additional treatment. 2 From Austin Retina Associates, Austin, Texas (CAH, RY); Eyesight Ophthalmic Services, Portsmouth, New Hampshire (KDB); Retina and Vitreous of Texas, Houston, Texas (EC); Stanford Byers Eye Institute, Palo Alto, California (DM). © 2020 Harper, Beck, Chang, Young, Moshfeghi; licensee SLACK Incorporated. This is an Open Access article distributed under the terms of the Cre- ative Commons Attribution 4.0 International (https://creativecommons.org/licenses/by/4.0). This license allows users to copy and distribute, to remix, transform, and build upon the article, for any purpose, even commercially, provided the author is at-tributed and is not represented as endorsing the use made of the work. Originally submitted July 30, 2020. Revision received July 30, 2020. Accepted for publication August 20, 2020. Dr. Moshfeghi received personal fees from Regeneron, Bayer, and Novartis, as well as grants from Genentech, outside the submitted work. The remaining authors report no relevant financial disclosures. Dr. Moshfeghi did not participate in the editorial review of this manuscript. Address correspondence to C. Armitage Harper III, MD, Retina Associates of Austin, Austin, TX; email: caharper@austinretina.com. doi: 10.3928/23258160-20201005-01

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