Comparison of Retinal Nonperfusion in Diabetic Macular Edema Treated with Brolucizumab Versus Aflibercept: A KINGFISHER Trial Analysis.
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- Also identified by DOI 10.1016/j.ajo.2026.07.041.
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Abstract
To compare longitudinal changes in retinal nonperfusion in diabetic macular edema (DME) patients treated with brolucizumab versus aflibercept over 52 weeks using ultrawidefield fluorescein angiography (UWF-FA) data from the KINGFISHER clinical trial. post hoc analysis from the KINGFISHER trial, (ClinicalTrials.gov Identifier: NCT03917472), a multicenter, masked clinical trial. Out of 517 participants in the KINGFISHER study, 164 had available baseline UWF-FA. 43 cases were excluded due to the presence of laser photocoagulation scar, and 30 cases were excluded due to poor image quality leaving a subset of 91 cases for nonperfusion assessment, of which 59 cases were included in the brolucizumab group, and 32 cases were included in the aflibercept group. Retinal nonperfusion was assessed from UWF-FA images at baseline, 24 weeks, and 52 weeks in patients treated monthly with either brolucizumab or aflibercept therapy. Images were graded by two independent graders for nonperfusion areas in three retinal regions: the panretina (TAR area), the posterior pole zone (a 15 mm diameter circle centered on the fovea), and the peripheral zone (all areas within the TAR, but outside the 15 mm circle). Nonperfusion index (NPI) was computed in the different retinal regions. Changes in NPI across follow-up visits were analyzed and compared between the brolucizumab and aflibercept treated groups. Over 52 weeks, both brolucizumab and aflibercept demonstrated no statistically significant change in retinal nonperfusion indices across posterior, peripheral, and pan-retinal zones. The mean NPI showed slight numerical increases from baseline at week 52, but differences were not statistically significant (p>0.05). Additionally, Linear mixed-effects modeling indicated no statistically significant difference in longitudinal NPI changes between both treatment groups (p>0.05). In this treated cohort, NPI did not show a statistically significant change over 52 weeks in eyes receiving monthly brolucizumab or aflibercept, with no statistically significant difference detected between agents. The absence of significant reperfusion despite intensive VEGF inhibition may suggest non-VEGF-mediated mechanisms.