OSLI Retina

June 2019

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June 2019 · Vol. 50, No. 6 337 ■ C L I N I C A L S C I E N C E ■ Neurodevelopmental Outcomes Comparing Bevacizumab to Laser for Type 1 ROP Sarah Hilkert Rodriguez, MD, MPH; Colleen Peyton, PT, DPT; Katherine Lewis, MS; Bree Andrews, MD, MPH; Mark J. Greenwald, MD; Michael D. Schreiber, MD; Michael E. Msall, MD; Michael P. Blair, MD BACKGROUND AND OBJECTIVE: To evaluate neuro- developmental outcomes among infants treated for retinopathy of prematurity (ROP) at the authors' in- stitution. PATIENTS AND METHODS: Before-and-after retrospec- tive chart reviews identified 40 infants treated with laser and 46 treated with primary intravitreal bevaci- zumab (IVB). Primary outcomes were death, hearing loss, bilateral visual impairment (BVI), and cerebral palsy (CP); odds ratios (ORs) were calculated to de- termine factors associated with CP. Secondary out- comes were mean Bayley Scales of Infant and Tod- dler Development, Third Edition (BSID-III) scores. RESULTS: Overall, there were no significant differ- ences in primary outcome measures by treatment group. However, adjusted odds of BVI were signifi- cantly higher with laser compared to IVB (OR = 13.1; P = .038). Although IVB was not associated with CP, both hydrocephalus and BVI were strongly corre- lated with CP. Mean Bayley-III scores were similar when comparing nine laser-treated infants to 13 IVB-treated infants. CONCLUSIONS: Visual outcomes are an important as- pect of neurodevelopment. IVB was not associated with severe developmental disabilities and may pro- tect against vision loss in this analysis. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:337-343.] INTRODUCTION Severe retinopathy of prematurity (ROP) is a mark- er for neurocognitive impairment. 1 Even without un- favorable ocular outcomes, the relationship between severe ROP and non-visual disabilities persists. 2 In- fants with severe ROP have higher rates of develop- mental delay, and the same process that leads to se- vere ROP may simultaneously injure the developing brain. 3,4 Since the publication of the BEAT-ROP study, use of intravitreal bevacizumab (IVB) (Avastin; Ge- nentech, South San Francisco, CA) has become in- creasingly common in the treatment of ROP, with ad- ditional reports of superior structural and refractive outcomes compared to laser. 5-7 Yet this therapeutic modality remains controversial, largely due to con- cerns about neurodevelopment. 8,9 When used as systemic chemotherapy for glioblas- toma, bevacizumab has been linked to neurocogni- tive decline among patients in the RTOG 0825 trial. 10 However, this association was not reported in the AVAglio trial. 11 Although vascular endothelial growth factor (VEGF) is suppressed following IVB injections in premature infants, 12 the optimal VEGF level in neo- nates is unknown. Serum VEGF is also suppressed in adults after intravitreal injections, and treatment with IVB has been used in adults with ocular neovascular disorders for more than a decade. 13,14 Safety studies have focused on thromboembolic events, but even in elderly patients, anti-VEGF injections have not been associated with systemic effects. 15 From University of Chicago, Department of Ophthalmology and Visual Science, Chicago (SHR, KL, MJG, MPB); University of Chicago, Department of Therapy Services, Chicago (CP); University of Chicago, Section of Neonatology, Chicago (BA, MDS); University of Chicago, Section of Developmental and Behavioral Pediatrics, Chicago (MEM); and Retina Consultants, Ltd, Des Plaines, Illinois (MPB). Originally submitted June 15, 2018. Revision received November 16, 2018. Accepted for publication January 3, 2019. Presented at the American Association for Pediatric Ophthalmology and Strabismus annual meeting, March 18, 2018, in Washington, DC; and at the ROP Hot Topics meeting, October 31, 2018, in Chicago. Supported in part by the Illinois Society for the Prevention of Blindness. The study sponsor had no role in the study design, collection, analysis, interpreta- tion, writing the manuscript, or decision to submit for publication. Dr. Peyton is on the speakers bureau for General Movements Trust outside the submitted work. The remaining authors report no relevant financial disclo- sures. The authors would like to acknowledge Kristen Wroblewski, MS, Department of Public Health Sciences, for her assistance with statistics. Drs. Msall and Blair contributed equally to this manuscript as senior authors. Address correspondence to Michael P. Blair, MD, University of Chicago, 5841 S. Maryland Avenue, MC2114, Chicago, IL 60637; email: michaelblairmd@ gmail.com. doi: 10.3928/23258160-20190605-01

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