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

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.

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.

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).

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.