Predicting intravitreal treatment response using ultrawide-field angiographic biomarkers in diabetic retinopathy

Advances in Ophthalmology Practice and Research · Published 2025-10-25 · DOI 10.1016/j.aopr.2025.10.003

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Abstract

Background: Diabetic retinopathy (DR) is a sight-threatening retinal disease with pathological mediation by vascular endothelial growth factor (VEGF). Intravitreal anti-VEGF injections are commonly used to manage DR. Ultra-wide-field fluorescein angiography (UWF-FA) can assess DR severity and characterize the amount of non-perfused retina (non-perfusion area, NP), neovascularization (neovascular area, NV), and foveal avascular zone (FAZ). However, the association between anti-VEGF treatment and NP, NV, and FAZ characterized by UWF-FA is not well established. Methods: A retrospective, single-center cohort study involved eyes of patients with Type 1 or 2 diabetes mellitus with at least one UWF-FA image. The area of the FAZ, NP area, and NV area of UWF-FA images was calculated. Stepwise multivariate logistic regression was used to identify patient and eye-level factors that were significant predictors of FAZ, NP, and NV. Causal model analyses estimated intravitreal treatment effects on FAZ, NP, and NV over time. Results: The study included 705 eyes from patients with a mean (SD) age of 59.2 (13.2) years, and 56.3% were male. Eyes were treated with a mean (SD) of 5.6 (7.7) anti-VEGF and 0.63 (1.94) intravitreal steroid injections. Each incremental increase in Early Treatment Diabetic Retinopathy Study (ETDRS) severity of DR on initial presentation by clinical exam was associated with a 12.86 mm2 increase in total NP and a 0.73 mm2 increase in NV area. Anti-VEGF and steroid treatment had no significant impact on FAZ area. The presence of intravitreal steroid treatment was associated with an estimated decrease of −0.909 mm2 in total NV area (P = 0.009). Each additional anti-VEGF injection decreased NV area by −0.239 mm2 (P = 0.031). Any steroid use also led to an estimated −10.79 mm2 decrease in NP (P = 0.041). Each additional anti-VEGF injection was predictive of a −2.54 mm2 decrease in NP (P = 0.019). Each additional steroid injection was predictive of a −13.68 mm2 decrease in NP (P = 0.001). Conclusions: Intravitreal treatment was significantly associated with reduced NV and NP on UWF-FA. Intravitreal treatments were not predictive of FAZ changes. These findings suggest total retinal NV and NP areas may provide utility as UWF-FA biomarkers for assessing intravitreal treatment response.

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Publication details

Year
2025

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