Real-Time Photographic and Fluorescein Angiographic-Guided Management of Diabetic Retinopathy: Randomized PRIME Trial Outcomes.

Abstract

PURPOSE\nAssess the safety and efficacy 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).\n\n\nDESIGN\nProspective, randomized phase 2 trial (PRIME).\n\n\nMETHODS\nForty eyes with non-proliferative (NPDR) or proliferative DR (PDR) received monthly IAI until a ≥2-step DRSS improvement was achieved and were randomized (1:1) to DRSS-guided or PLI-guided management strategies, graded by a central reading center. Main outcome measures included safety as well as changes in DRSS and PLI.\n\n\nRESULTS\nThrough week 52 (W52), 95% of eyes achieved ≥2-step DRSS improvement. Following DRSS improvement, 97% required at least one PRN IAI. In eyes requiring PRN IAI and completing W52, 100% and 59% experienced DRSS worsening (p=0.01) in the DRSS- and PLI-guided arms. Through W52, mean PLI decreased 18.2% (p=0.49) and 54.6% (p<0.0001) in the DRSS- and PLI-guided arms. NPDR vs PDR eyes at baseline achieved ≥2-step DRSS improvement after a mean 4.9 and 3.6 IAI (p=0.03). Two eyes developed a PDR event at W52 following 5-months of quiescence.\n\n\nCONCLUSIONS\nThe randomized PRIME study analyzed 2 imaging-based biomarkers to guide PRN management with IAI of DR without DME: DRSS level and PLI. Within the context of this study with limitations, most patients required IAI re-treatment every 3-4 months and deterioration of PLI appeared to precede DRSS level worsening. Finally, these findings reaffirm that close clinical follow-up is important even among eyes that achieve substantial DRSS-improvements with apparently quiescent disease.