A Phase 1 Dosing Study of Bevacizumab for ROP: 12-month Ocular Outcomes
Eric R. Crouch, MD; David K. Wallace, MD; Raymond T. Kraker, MSPH; Michael X. Repka, MD; Janine E. Collinge, MD; Michael E. Gray, MD; Paul G. Steinkuller, MD; Don L. Bremer, MD
Jaeb Center for Health Research
Introduction: Infants with type 1 ROP were enrolled into a masked, multi-center, phase 1 dose de-escalation study and treated initially with doses of 0.25 mg, 0.125 mg, 0.063 mg, or 0.031 mg of bevacizumab. Additional treatment after 4-weeks was at investigator discretion. Ocular outcomes at 12-months corrected age are reported.
Methods: Infants were examined at 12-months corrected age.
Results: Forty-five of 58 infants (76%) completed the outcome exam. Of 44 study eyes with a cycloplegic refraction, 6 (14%) had myopia > -5.00D spherical equivalent [SE]) and 2 (5%) had hyperopia >+4.00D SE. Mean SE refractive error was -0.88D. Abnormalities of the cornea, lens, or anterior segment were reported in 2 (4%), 1 (2%), and 1 (2%) eye(s), respectively. Optic nerve atrophy was identified in 6 (13%) eyes; 1 (2%) eye had a total retinal detachment. Strabismus at near fixation was present in 13 infants (29%), 7 (16%) had nystagmus and 3 (7%) had amblyopia. Of 44 study eyes assessed for fixation behavior, 36 (82%) had central, steady, and maintained fixation behavior.
Discussion: In this study of low dose bevacizumab, the rates of high myopia, strabismus, nystagmus, and other ocular findings at one year were low and consistent with rates reported for higher doses.[1-3]
Conclusion: A larger comparative study with longer follow-up will be required to better assess the relative risks for developing ocular co-morbidities in infants receiving a lowest effective dose of bevacizumab for Type 1 ROP as determined by this phase 1 study.
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