Diabetic Retinopathy Severity on Ultra-Widefield Fluorescein Angiography versus Color Photography and Association...

To evaluate the potential benefits of ultra-widefield (UWF) fluorescein angiography (FA) versus color photography in assessing the risk of diabetic retinopathy (DR) worsening.

Exploratory analysis of a longitudinal observational study (Protocol AA).

Participants with ≥1 eye having nonproliferative DR at baseline.

For each UWF-color and UWF-FA image, the extent and severity of DR lesions within the ETDRS 7-field area ("masked") and the full image area ("unmasked") were determined. Diabetic retinopathy severity levels were graded for each combination of modality and masking condition using the ETDRS Diabetic Retinopathy Severity Scale (DRSS). Associations between baseline UWF-color and UWF-FA DR severity with disease worsening were evaluated and compared.

Disease worsening over 4 years, defined as ≥2-step DRSS worsening on masked UWF-color or receipt of DR treatment.

Among the 768 eyes, DRSS agreement between masked UWF-color versus masked or unmasked UWF-FA at each visit was fair to moderate (range for κ: 0.34-0.53). Ultra-widefield FA identified more severe DR than masked UWF-color in 57% of the masked UWF-FA images and 62% of the unmasked. Over 4 years, disease worsening was more common in eyes with a more severe grade on masked UWF-FA than masked UWF-color for hemorrhages and/or microaneurysms (47% vs. 37%; P = 0.04), intraretinal microvascular abnormalities (IRMA) (50% vs. 36%; P = 0.007), and new vessels/neovascularization elsewhere (NVE) (57% vs. 39%; P < 0.003), and on unmasked UWF-FA for IRMA (49% vs. 35%; P = 0.008) and NVE (58% vs. 38%; P < 0.001). A greater risk of disease worsening was also associated with more severe DRSS level on masked (50% vs. 30%; P < 0.001) and on unmasked (50% vs. 28%; P < 0.001) UWF-FA compared with masked UWF-color.

This analysis highlights important differences between UWF-color and UWF-FA in assessing DR severity and predicting disease progression over time. Ultra-widefield FA appears to offer a more accurate risk assessment of future DR worsening. These findings support the integration of UWF-FA findings into the existing grading scales and the development of supplemental DRSS grading criteria that incorporate the additional prognostic information provided by angiographic imaging.

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.