Study Identifies Two Biomarkers of Retinal Ischemic Burden on Macular OCT-A

While fluorescein angiography can be used to characterize retinal nonperfusion in patients with diabetes, researchers recently looked for a less invasive alternative. They found two OCT-A-derived metrics that correlated to retinal nonperfusion on UWF-FA: geometric perfusion deficits in the deep capillary plexus (calculated as the proportion of retinal areas located ≥30μm from the nearest perfused capillary on OCT-A in the deep capillary plexus) and FAZ enlargement. These images, from a previous study by the same research team, shows the researchers’ method of calculating geometric perfusion deficit from 3x3mm en face full-slab OCT-A scans. The final set of images (M-O) show GPD maps highlighting areas located at least 30µm away from the nearest capillary (red), with the FAZ manually delineated and shown in white. Photo: Kakihara S, et al. Invest Ophthalmol Vis Sci 2025;66:14:45. Click image to enlarge. A single-center study conducted at Northwestern University in Chicago recently reported that two macular OCT angiography (OCT-A) biomarkers—geometric perfusion deficits in the deep capillary plexus (GPDd) and foveal avascular zone (FAZ) enlargement—correlate with retinal nonperfusion on ultra-widefield fluorescein angiography (UWF-FA) in distinct ways. GPDd strongly reflected ischemic burden across posterior, peripheral and total retinal regions, while FAZ enlargement aligned specifically with posterior ischemia. Since retinal nonperfusion may predict progression of diabetic retinopathy (DR), these findings suggest macular OCT-A may be a noninvasive tool to assess ischemia and stratify risk in this population.Published in American Journal of Ophthalmology a few days ago, the prospective, cross-sectional, observational study enrolled 159 eyes from 112 adults with type 1 or type 2 diabetes across the full spectrum of DR severity, recruited over two years. All participants underwent comprehensive ophthalmic evaluation, including ETDRS BCVA, lens status, axial length, spectral-domain OCT, UWF pseudo-color photography and UWF-FA, as well as macular OCT-A. The study authors defined geometric perfusion deficits in the deep capillary plexus “as the proportion of retinal areas located ≥30μm from the nearest perfused capillary on OCT-A in the deep capillary plexus.”The data showed that macular OCT-A-derived perfusion deficits were significantly associated with retinal nonperfusion on UWF-FA across all regions examined. In fully adjusted mixed-effects models, higher GPDd correlated with greater posterior nonperfusion, peripheral nonperfusion and total nonperfusion. In contrast, FAZ enlargement was independently linked only to posterior nonperfusion and showed no association with peripheral or total nonperfusion.Model comparisons reinforced these region-specific patterns. Adding deep capillary perfusion deficits improved model fit for posterior, peripheral and total nonperfusion, while FAZ enlargement enhanced model fit only for posterior nonperfusion, including when combined with GPDd. “These results suggest that FAZ enlargement specifically reflects posterior ischemia, whereas GPDd serves as a robust biomarker of global ischemic burden across the entire retina,” the researchers explained in their paper. They further noted that these findings “align with prior studies that demonstrated the strong correlation between GPDd and global retinal ischemia, supporting its use as a comprehensive OCT-A-derived biomarker of ischemic burden.” In addition, prior research has correlated FAZ enlargement with DR severity and loss of visual function, highlighting “the complementary roles of these two macular OCT-A-derived biomarkers.”Systemic factors also showed region-specific associations in this study: higher HbA1c related to greater posterior nonperfusion, and longer diabetes duration related to more peripheral and total nonperfusion. This suggests “that posterior nonperfusion more closely reflects current metabolic status, whereas peripheral and total nonperfusion are impacted by cumulative disease burden,” the authors stated in their paper.“From a clinical perspective,” they concluded, “these findings suggest that macular OCT-A biomarkers may provide complementary information about retinal ischemic burden without the need for dye injection.” Particularly, the authors wrote, “GPDd may serve as a practical indicator of global ischemia that could help guide the use of UWF-FA or closer clinical follow-up, although prospective validation is required.”Click here for the journal source. Kakihara S, Busza AM, Duffy BV, et al. Macular OCTA biomarkers predict regional retinal nonperfusion patterns on ultra-widefield angiography in diabetes. Am J Ophthalmol. March 28, 2026. [Epub ahead of print]  This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.