Study Identifies Optimal OCT-A Metrics for DR Progression

Prompt evaluation and close monitoring, particularly of the retinal microvasculature, is essential for minimizing the risk of permanent vision loss in patients with diabetic retinopathy (DR). Obtaining this information has traditionally involved gold-standard fluorescein angiography, but interest in a noninvasive alternative—optical coherence tomography angiography (OCT-A)—has grown in recent years. In an Investigative Ophthalmology and Vision Science paper published this month, researchers at Northwestern University explored the OCT-A metrics that best capture early progression of nonperfusion in DR. Read on for their findings.1The prospective study included 208 patients with diabetes (320 eyes) who underwent 3x3mm macular OCT-A at baseline, six months and 12 months. The researchers used registered averaged images to quantify several OCT-A metrics and graded eyes as non-referable or referable. Based on OCT-A data from 709 clinic visits over a one-year period, they reported that referable DR, longer diabetes duration and hypertension were independently associated with higher geometric perfusion deficits. Neither fluorescein angiography nor OCT-A is all-encompassing when it comes to evaluating retinal vessels. FA, for example, offers a widefield view of the peripheral retina, while OCT-A’s strength lies in its detailed assessment of the central macula. Experts say using both modalities in a complementary fashion may offer the best diagnostic approach.2 In these images from the study, figures A and B show averaged OCT-A images of the superficial capillary plexus (SCP) and deep capillary plexus (DCP), respectively. These images were then binarized (C, D), wherein vessels appear as white areas and the background as black. These are used to calculate vessel density by measuring the proportion of vessel area relative to the total image area. In E and F, skeletonized images of the SCP and DCP layers are shown, where vessel structures are reduced to single-pixel-wide lines while preserving their original shape. This processing allows for the quantification of vessel length density by measuring the total vessel length. Finally, figures G and H show the SCP and DCP layers processed to identify areas that are at least 30µm away from the nearest vessel (red areas). These images are used to calculate geometric perfusion deficits by analyzing the perfusion-free areas relative to the total area. Photo: Kakihara S, et al. Invest Ophthalmol Vis Sci 2025;66:11:49. Click image to enlarge. Eyes with referable DR demonstrated increased geometric perfusion deficits in the deep capillary plexus at six months and one year. This was the only OCT-A metric that changed significantly at six months and was therefore deemed a “particularly sensitive biomarker of progressive microvascular compromise.”In non-referable eyes, decreased vessel density in the superficial capillary plexus at one year was the only significant change, suggesting that microvascular parameters may progress differently as DR advances.The researchers emphasized the value of incorporating metrics that prioritize small vessel changes when monitoring DR. They also stated in their paper that these findings may have important implications for clinical trials.“Because geometric perfusion deficit in the deep capillary plexus was the earliest OCT-A metric to show progression in referable DR, it may help identify eyes that require closer surveillance,” they concluded. “With further confirmation in larger cohorts, [this metric] could potentially serve as an objective exploratory endpoint in trials, and it could be instrumental in monitoring microvascular progression in referable DR.”Click here for the journal source. 1. Kakihara S, Zhuang K, AbdelSalam M, Yamaguchi TC. The importance of matching optical coherence tomography angiography metrics to diabetic retinopathy severity for detecting progression. Invest Ophthalmol Vis Sci 2025;66:11:49.2. Enders C, Baeuerle F, Lang GE, et al. Comparison between findings in optical coherence tomography angiography and in fluorescein angiography in patients with diabetic retinopathy. Ophthalmologica 2020;243:1:21-26. 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.