Yu HJ, Ehlers JP, Sevgi DD, et al. - In this prospective, randomized phase 2 trial (PRIME), researchers tested the effectiveness and safety of as needed (PRN) intravitreal aflibercept injections (IAI) in managing diabetic retinopathy (DR) guided by real-time DR severity scale (DRSS) level or panretinal leakage index (PLI) assessment among eyes without diabetic macular edema (DME). Forty eyes with non-proliferative (NPDR) or proliferative DR (PDR) obtained monthly IAI until a ≥ 2-step DRSS improvement was accomplished and were randomized (1:1) to DRSS-guided or PLI-guided management strategies, graded by a central reading center. The randomized PRIME study analyzed 2 imaging-based biomarkers to direct DR without DME's PRN management with IAI: DRSS level and PLI. Within the context of this limited study, most patients needed IAI re-treatment every 3-4 months and deterioration of PLI appeared to precede worsening of DRSS levels. Finally, these findings reaffirm that even among eyes that achieve substantial DRSS improvements with an apparently quiescent disease, close clinical follow-up is necessary.