A Prospective Randomized Comparative Dosing Trial of Ranibizumab in Bevacizumab-Resistant Diabetic Macular Edema The REACT Study

Purpose: To assess the efficacy of ranibizumab for persistent diabetic macular edema (DME) previously treated with bevacizumab and compare monthly versus treat-and-extend (TREX) dosing. Design: Twelve-month open-label prospective, randomized, comparative dosing study. Participants: Twenty-seven participants with persistent foveal-involving DME recently treated with bevacizumab. Methods: All participants were to receive 3 initial monthly 0.3-mg ranibizumab injections before randomization to monthly (n = 15) or TREX (n = 12) injection protocols over 12 months. The treatment interval was extended by 2 weeks up to a maximum interval of 12 weeks in the TREX group if central subfield thickness (CST) was 300 mu m or less or complete absence of intraretinal or subretinal fluid on the macular cube was observed. The follow-up interval was decreased by 2 weeks if CST increased to 300 mu m or more with associated intraretinal or subretinal fluid, or both. Main Outcome Measures: Change in Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA), CST, and adverse events. Results: Before study enrollment, participants received an average of 8.6 bevacizumab injections. At month 12, mean ETDRS BCVA improved by +5.3 letters (P < 0.05) and mean CST decreased by 99.6 mu m (P < 0.01) in all patients. At study exit, 18.5% of patients gained 3 lines or more of vision and 3.7% of patients lost 3 lines or more. Patients treated via the TREX protocol gained 8.4 letters and CST decreased by 120.2 mu m, whereas those treated by monthly injection gained 2.7 letters and CST decreased by 83.1 mu m at month 12. Conclusions: After conversion to ranibizumab in eyes with persistent DME refractory to bevacizumab, significant functional and anatomic improvements were noted. Visual and anatomic outcomes were similar in TREX and monthly treatment protocols. (C) 2017 Published by Elsevier Inc. on behalf of the American Academy of Ophthalmology