Longitudinal Quantitative Ultrawidefield Angiographic Features in Diabetic Retinopathy Treated with Aflibercept from the Intravitreal Aflibercept as Indicated by Real-Time Objective Imaging to Achieve Diabetic Retinopathy Improvement Trial

Objective: To report longitudinal trends of quantitative ultrawidefield fluorescein angiography (qUWFA) biomarkers in the Intravitreal Aflibercept as Indicated by Real -Time Objective Imaging to Achieve Diabetic Retinopathy Improvement (PRIME) diabetic retinopathy (DR) clinical trial. Design: Post hoc analysis of the PRIME prospective randomized DR clinical trial comparing intravitreal aflibercept treatment based on the DR severity score (DRSS) or quantitative leakage index for DR improvement (ClinicalTrials.gov identifier: NCT03531294). Participants: Patients were enrolled with a DRSS level of 47A to 71A and best -corrected visual acuity of 20/ 800 or better. Key exclusion criteria were previous intravitreal injection, panretinal photocoagulation, vitrectomy, central -involving macular edema, or vitreous hemorrhage. Methods: A previously validated, machine learning -based qUWFA analysis platform was used for panretinal leakage index assessment and differentiation of generalized and perivascular leakage phenotypes. Additionally, microaneurysm count and ischemic index were quantified in panretinal and macular regions. The trends in these biomarkers and therapeutic response were studied over 1 year. Main Outcome Measures: Longitudinal trends of qUWFA biomarkers. The impact of these qUWFA metrics on treatment response was assessed by studying their associations with time to 2 -step DRSS improvement and number of treatment -free days. Results: Forty eyes from 40 subjects with DR were enrolled. Lower baseline generalized leakage was noted in eyes that attained the 2 -step DRSS improvement in < 16 weeks (1.9% vs. 2.8%; P = 0.026). Baseline macular perivascular-generalized leakage ratio had a significant correlation with the number of treatment -free days (r = 0.4; P = 0.012). At the end of 1 year, therapy significantly reduced the mean panretinal (3.9% vs. 5.8%; P = 0.002) and macular (6.2% vs. 12.2%; P = 0.008) generalized leakage indices compared with baseline, as well as the mean panretinal perivascular leakage index (1.5% vs. 2.3%; P = 0.002). The mean panretinal ischemic index demonstrated a small but likely clinically insignificant decrease from 12.5% at baseline to 11.6% at year 1 (P = 0.016). Conclusions: Down -trending leakage indices and microaneurysm counts were demonstrated over 1 year of anti-VEGF therapy. At baseline, DR eyes with lower generalized leakage responded to therapy more rapidly. Eyes with greater perivascular leakage relative to generalized leakage showed a longer -lasting anti-VEGF treatment response. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. Ophthalmology Retina 2024;8:116-125 (c) 2023 by the American Academy of Ophthalmology.