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AimTo evaluate the potential of radiomics-based ultra-widefield fluorescein angiography (UWFA)-derived imaging biomarkers in retinal vascular disease for predicting therapeutic durability of intravitreal aflibercept injection (IAI).MethodsThe Peripheral and Macular Retinal Vascular Perfusion and Leakage Dynamics in Diabetic Macular Edema and Retinal Venous Occlusions During Intravitreal Aflibercept Injection (IAI) Treatment for Retinal Edema (PERMEATE) study prospectively evaluated quantitative UWFA dynamics in diabetic macular oedema or macular oedema secondary to retinal vascular occlusion. 27 treatment-naïve eyes were treated with 2 mg IAI q4 weeks for the first 6 months, and then administered q8 weeks. Morphological and graph-based attributes were used to model the spatial distribution of leakage areas, while tortuosity measures were used to model the vessel network disorder. Eyes were grouped based on functional tolerance of the first 8-week treatment interval challenge. ‘Non-rebounders’ (N=15) maintained/improved best-corrected visual acuity (BCVA) following the 8-week challenge. ‘Rebounders’ (N=12) exhibited worsened BVCA. The image biomarkers were used with a machine learning classifier to preliminarily evaluate their ability to predict BCVA stability.ResultsTwo new UWFA image-derived biomarkers were identified and extracted. The cross-validated area under the receiver operating characteristic curve (AUC) was 0.77±0.14 using baseline leakage distribution features and 0.73±0.10 for the UWFA baseline tortuosity measures. Additionally, the change in vascular tortuosity between month 4 and baseline yielded an AUC of 0.73±0.08. Three baseline clinical features of letter score, macular volume and central subfield thickness yielded a corresponding AUC of 0.42±0.09.ConclusionsTwo computer-extracted UWFA radiomics-based descriptors were identified as potential biomarkers for predicting treatment durability and tolerance of longer treatment intervals. Conventional treatment parameters were not significantly different between these same groups.