@article {1655733,
	title = {Low- and Very Low-Dose Bevacizumab for Retinopathy of Prematurity: Reactivations, Additional Treatments, and 12-Month Outcomes},
	journal = {Ophthalmology},
	volume = {129},
	number = {10},
	year = {2022},
	month = {2022 10},
	pages = {1120-1128},
	abstract = {PURPOSE: Low-dose and very low-dose intravitreal bevacizumab (IVB) have been reported to be successful in short-term treatment of type 1 retinopathy of prematurity (ROP), down to an initial dose of 0.004 mg. We now report 12-month outcomes for these infants. DESIGN: Masked, multicenter, dose de-escalation study. PARTICIPANTS: One hundred twenty prematurely born infants with type 1 ROP. METHODS: A cohort of 120 infants with type 1 ROP in at least 1 eye from 2 sequential dose de-escalation studies of low-dose IVB (0.25 mg, 0.125 mg, 0.063 mg, and 0.031 mg) or very low-dose IVB (0.016 mg, 0.008 mg, 0.004 mg, and 0.002 mg) to the study eye; the fellow eye (if also type 1) received 1 dose level higher of IVB. After primary success or failure at 4 weeks, clinical management was at investigator discretion, including all additional treatment. MAIN OUTCOME MEASURES: Reactivation of severe ROP by 6 months corrected age, additional treatments, retinal and other ocular structural outcomes, and refractive error at 12 months corrected age. RESULTS: Sixty-two of 113 study eyes (55\%) and 55 of 98 fellow eyes (56\%) received additional treatment. Of the study eyes, 31 (27\%) received additional ROP treatment, and 31 (27\%) received prophylactic laser therapy for persistent avascular retina. No trend toward a higher risk of additional ROP treatment related to initial IVB doses was found. However, time to reactivation among study eyes was shorter in eyes that received very low-dose IVB (mean, 76.4 days) than in those that received low-dose IVB (mean, 85.7 days). At 12 months, poor retinal outcomes and anterior segment abnormalities both were uncommon (3\% and 5\%, respectively), optic atrophy was noted in 10\%, median refraction was mildly myopic (-0.31 diopter), and strabismus was present in 29\% of infants. CONCLUSIONS: Retinal structural outcomes were very good after low- and very low-dose IVB as initial treatment for type 1 ROP, although many eyes received additional treatment. The rate of reactivation of severe ROP was not associated with dose; however, a post hoc data-driven analysis suggested that reactivation was sooner with very low doses.},
	keywords = {Angiogenesis Inhibitors, Bevacizumab, Gestational Age, Humans, Infant, Infant, Newborn, Intravitreal Injections, Laser Coagulation, Retinopathy of Prematurity, Retrospective Studies},
	issn = {1549-4713},
	doi = {10.1016/j.ophtha.2022.05.019},
	author = {Freedman, Sharon F and Hercinovic, Amra and Wallace, David K and Kraker, Raymond T and Li, Zhuokai and Bhatt, Amit R and Boente, Charline S and Crouch, Eric R and Hubbard, G Baker and Rogers, David L and Vanderveen, Deborah and Yang, Michael B and Cheung, Nathan L and Cotter, Susan A and Holmes, Jonathan M and Pediatric Eye Disease Investigator Group}
}
