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Observational Study
. 2025 Jun 2;66(6):5.
doi: 10.1167/iovs.66.6.5.

Posterior Retinal Ischemia Correlates With Vision in Patients With Diabetes

Affiliations
Observational Study

Posterior Retinal Ischemia Correlates With Vision in Patients With Diabetes

Shinji Kakihara et al. Invest Ophthalmol Vis Sci. .

Abstract

Purpose: The purpose of this study was to investigate whether the topographic location of retinal non-perfusion influences visual function, specifically low luminance visual acuity (LLVA) and best-corrected visual acuity (BCVA), in individuals with diabetes.

Methods: In this cross-sectional observational study, individuals with diabetes across the spectrum of diabetic retinopathy (DR) severity were enrolled. LLVA and BCVA were measured according to the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol, with a 2.0-log unit neutral density filter for LLVA. Retinal ischemia was evaluated using ultra-widefield fluorescein angiography (UWF-FA) to manually quantify non-perfusion within (posterior ischemia) and outside (peripheral ischemia) the ETDRS seven fields. Macular ischemia was assessed by optical coherence tomography angiography (OCTA) using geometric perfusion deficits (GPDs) in both the superficial and deep capillary plexus (DCP). Associations between visual acuity and various explanatory variables, focusing on retinal ischemic parameters were assessed with linear mixed models.

Results: A total of 181 eyes from 126 patients without diabetic macular edema were analyzed. Increasing DR severity reduced both BCVA and LLVA. After adjusting other explanatory variables, age and posterior ischemia (estimate = -0.46, P = 0.046) were significant for LLVA. In contrast, age, sex, posterior ischemia (estimate = -0.50, P = 0.009), and GPD-DCP (estimate = -0.25, P = 0.049) were statistically significant for BCVA.

Conclusions: Retinal ischemia's topographic location differentially affects visual function in diabetes. Posterior ischemia predominantly impacts LLVA, whereas both macular and posterior ischemia contribute to BCVA decline. These results highlight the importance of assessing retinal ischemia beyond the macula to better understand visual function deficits in patients with diabetes.

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Conflict of interest statement

Disclosure: S. Kakihara, None; A. Busza, None; T.C. Yamaguchi, Boehringer Ingelheim (E); A.A. Fawzi, Regeneron (C), Roche/Genentech (C), Boehringer Ingelheim (C), RegenXbio (C), 3Helix (C)

Figures

Figure 1.
Figure 1.
Image processing pipeline for geometric perfusion deficit analysis in OCTA. This figure provides an overview of the image processing pipeline used for the quantitative analysis of geometric perfusion deficits (GPD) in OCTA images from the superficial capillary plexus (SCP), deep capillary plexus (DCP), and full retina slab. The workflow begins with the averaging of exported images for each slab to enhance vessel visualization and reduce noise. A dedicated processing algorithm extracts GPD metrics by segmenting and analyzing perfusion characteristics across different retinal layers. This semi-automated approach ensures a standardized assessment of microvascular alterations, facilitating reliable quantification of ischemic changes in the macula. Among the quantified GPD values, those derived from the SCP and DCP are used for the analysis in this study.
Figure 2.
Figure 2.
Topographic analysis of retinal ischemia using ultra-widefield fluorescein angiography and OCTA-based geometric perfusion deficits. Ultra-widefield fluorescein angiography (UWF-FA) illustrating the regions used to calculate four parameters that reflect the topographic distribution of retinal ischemia: GPD-SCP, GPD-DCP, posterior ischemia, and peripheral ischemia. A 3 × 3 mm area centered on the fovea was imaged using optical coherence tomography angiography (OCTA), from which geometric perfusion deficits in the superficial and deep capillary plexuses of the macula were calculated from the SCP and DCP slabs, respectively. The area within the yellow square corresponds to the specific region evaluated by OCTA for layer-specific ischemia. The nonperfusion index within the ETDRS seven fields was manually quantified as the proportion of retinal nonperfusion within the seven white circles that define the ETDRS seven fields, and it was considered posterior ischemia. The nonperfusion index outside the ETDRS seven fields was manually quantified as the proportion of retinal nonperfusion within the area bounded by the green dashed line and located outside the ETDRS seven fields, and it was considered peripheral ischemia. To account for the projection of the three-dimensional retina onto a two-dimensional image, the software corrected for magnification artifacts and transformed the marked regions into a stereographic projection, enabling accurate measurement of nonperfused areas.

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