Real-Time Diabetic Retinopathy Severity Score Level versus Ultra-Widefield Leakage Index-Guided Management of Diabetic Retinopathy: Two-Year Outcomes from the Randomized PRIME Trial.

Hannah J Yu,Jamie L Reese,Sunil K Srivastava,Charles C Wykoff,Margaret O’Connell,Justis P Ehlers,Duriye Damla Sevgi

doi:10.3390/jpm11090885

Abstract

The prospective PRIME trial applied real-time, objective imaging biomarkers to determine individualized retreatment needs with intravitreal aflibercept injections (IAI) among eyes with diabetic retinopathy (DR). 40 eyes with nonproliferative or proliferative DR without diabetic macular edema received monthly IAI until a DR severity scale (DRSS) level improvement of ≥2 steps was achieved. Eyes were randomized 1:1 to DRSS- or PLI- guided management. At the final 2-year visit, DRSS level was stable or improved compared to baseline in all eyes, and mean PLI decreased by 11% (p = 0.73) and 23.6% (p = 0.25) in the DRSS- and PLI-guided arms. In both arms, the percent of pro re nata (PRN) visits requiring IAI was significantly higher in year 2 versus 1 (p < 0.0001). The percent of PRN visits receiving IAI during year 1 was significantly correlated with the percent of PRN visits with IAI during year 2 (p < 0.0001). Through week 104, 77.4% of instances of DRSS level worsening in the DRSS-guided arm were preceded by or occurred alongside an increase of PLI. Overall, consistent IAI re-treatment interval requirements were observed longitudinally among individual patients. Additionally, PLI increases appeared to precede DRSS level worsening, highlighting PLI as a valuable biomarker in the management of DR.

Highlights

Introduction iationsDiabetic retinopathy (DR) is a leading cause of preventable vision loss [1]
The randomized PRIME trial explored the use of real-time diabetic retinopathy severity scale (DRSS) and panretinal leakage index (PLI) assessments to determine re-treatment decisions for patients with diabetic retinopathy (DR) without center-involved diabetic macular edema (DME)
Through week 104, all subjects in both the DRSS- and PLI-guided arms demonstrated either stable or improved DRSS compared to baseline, with all subjects requiring at least one pro re nata (PRN)

Summary

Introduction

Introduction iationsDiabetic retinopathy (DR) is a leading cause of preventable vision loss [1]. In the setting of diabetic macular edema (DME) with visual loss, multiple studies have demonstrated the remarkable visual and anatomic value of consistent anti-vascular endothelial growth factor (VEGF) pharmacotherapy initiated early in the disease process [2,3,4,5]. Prospective studies involving eyes with DR without DME, both proliferative DR (PDR) [6,7,8,9] and nonproliferative DR (NPDR) [10,11], have repeatedly demonstrated clinically meaningful anatomic benefits with repeated anti-VEGF treatment compared to laser or observation. While fixed interval anti-VEGF dosing among a population has frequently been employed in clinical trials [2,3,10], this is rarely applied to routine clinical practice. Specific examination and/or imaging-based biomarkers of disease activity are typically applied to guide dosing frequency using an individualized, patient-centric approach.

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