Longitudinal quantitative ultra-widefield fluorescein angiography leakage dynamics in patients with uveitic macular edema following intravitreal anti–IL-6 therapy with vamikibart

Abstract

Purpose : To evaluate quantitative ultra-widefield fluorescein angiography (UWFA) leakage dynamics in the DOVETAIL phase 1 clinical trial of intravitreal (IVT) vamikibart (anti–interleukin-6 [IL-6] monoclonal antibody; RG6179) in patients with uveitic macular edema (UME).

Methods : DOVETAIL is a phase 1, multicenter, nonrandomized, open-label, multiple ascending dose study to investigate the safety, tolerability, efficacy and pharmacokinetic/pharmacodynamic profile of IVT vamikibart in patients with diabetic macular edema and UME. Patients with UME (n=37) received 3 monthly IVT injections and were followed after treatment until week 36. Longitudinal assessment of leakage on UWFA images was conducted using a machine-learning augmented feature extraction platform with subsequent expert certified reader validation and segmentation correction (as needed). Leakage index was calculated as the proportion of retinal leakage (ie hyperfluorescence) within the analyzable retina area. This analysis focused on retinal leakage and did not evaluate optic nerve leakage. In addition to panretinal assessment, zonal analysis was also conducted (posterior pole, periphery). Preliminary findings are presented.

Results : UWFA was performed on 33 eyes as part of the study. Quantitative angiographic analysis was able to be successfully completed for all 33 eyes. Variable leakage patterns were noted based on the underlying UME angiographic phenotype. There was a robust reduction in overall quantitative leakage index, including in the posterior pole and retinal periphery (Fig 1).

Conclusions : These promising preliminary results confirm the feasibility of quantitative UWFA leakage analysis and indicate a potential reduction in quantitative leakage parameters in eyes with UME undergoing anti–IL-6 treatment. Future analyses are needed to further characterize these changes in the entire study population as well as a more detailed assessment to investigate the effect of vamikibart anti–IL-6 treatment on UME severity and functional outcomes.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.

 

Fig 1. (A) Representative case (n=1) highlighting changes in leakage index (proportion of leakage in analyzable retina) over time; (B) Baseline UWFA image of representative case during late phase of image acquisition (leakage overlay in yellow); (C) UWFA image at day 42; (D) UWFA image at day 84; (E) UWFA image at day 140.