Impact of Baseline Retinal Non-Perfusion (NP) and Leakage on Center-Involved Diabetic Macular Edema (CI-DME) and/or Vision-Threatening Complications (VTC) in Non-Proliferative Diabetic Retinopathy (NPDR) in the PANORAMA Trial

Abstract

Purpose : Impact of baseline retinal NP and leakage on rates of CI-DME and/or VTC (PDR/anterior segment neovascularization) was assessed in patients receiving intravitreal aflibercept injections (IAI) or sham injections through 100 weeks in PANORAMA.

Methods : This post hoc analysis included patients with moderately severe to severe NPDR (Diabetic Retinopathy Severity Scale [DRSS] 47–53) without baseline DME who received IAI 2 mg q16 weeks (N=135) or q8 weeks (PRN dosing in year 2; N=134) (both after initial loading doses) or sham (N=133). IAI groups were combined. Baseline NP (mm²) was analyzed in 4 groups: G1: =0, n=201; G2: >0–≤0.24, n=52; G3: >0.24–≤0.66, n=53; G4: >0.66, n=51. Baseline leakage area (mm²) was analyzed by quartile: Q1: ≤10.20, n=98; Q2: >10.20–≤19.76, n=97; Q3: >19.76–≤30.41, n=97; Q4: >30.41, n=97.

Results : Proportions of patients who developed CI-DME/VTC across increasing baseline NP or leakage groups increased with sham but were similar with IAI (Figures 1, 2). Risk of developing CI-DME/VTC increased with baseline NP area (per 1 mm² increase) with sham, hazard ratio (HR): 1.32 (95% confidence interval [CI]: 1.06, 1.64; P=0.0125) but not with IAI, 1.06 (0.88, 1.27; P=0.5669). Results were similar for impact of baseline NP on risk of CI-DME alone, HR (95% CI): 1.32 (1.04, 1.67) with sham and 0.95 (0.68, 1.33) with IAI; and VTC alone, 1.44 (1.08, 1.92) with sham and 1.10 (0.89, 1.38) with IAI. Similarly, risk of CI-DME/VTC increased with baseline leakage area (per 1 mm² increase) with sham, HR 1.05 (95% CI: 1.02, 1.07; P<0.0001) but not IAI, 1.03 (1.00, 1.05; P=0.0550). The HR (95% CI) for impact of baseline leakage on risk of CI-DME alone was 1.02 (0.99, 1.05) with sham and 1.03 (1.00, 1.07) with IAI; and for VTC alone was 1.08 (1.04, 1.12) with sham and 1.00 (0.96, 1.04) with IAI. Sham but not IAI was associated with a lower proportion of patients with ≥2-step DRSS improvement and higher proportion with ≥2-step DRSS worsening with increasing baseline NP and leakage areas, although the trend was not significant for baseline NP.

Conclusions : Increasing baseline retinal NP and leakage areas were associated with increased rates of CI-DME/VTC in the sham group. This association was not observed in the IAI-treated group.

This is a 2021 ARVO Annual Meeting abstract.