Peripheral arterial disease is associated with retinal fluid and microvascular alterations in type 2 diabetes

doi:10.4239/wjd.122779

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World Journal of Diabetes

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1948-9358

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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Retrospective Cohort Study

Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Diabetes. Sep 15, 2026; 17(9): 122779
Published online Sep 15, 2026. doi: 10.4239/wjd.122779

Peripheral arterial disease is associated with retinal fluid and microvascular alterations in type 2 diabetes

Jee Myung Yang, Jiehoon Kwak, Se Hee Min, Sang Uk Choi, Jaeyu Park, Dong Keon Yon, Joo Yong Lee, June-Gone Kim, Young Hee Yoon, Yoon Jeon Kim

Jee Myung Yang, Jiehoon Kwak, June-Gone Kim, Young Hee Yoon, Yoon Jeon Kim, Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, South Korea

Se Hee Min, Department of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, South Korea

Sang Uk Choi, Department of Ophthalmology, Smart Eye Clinic, Gwacheon-si 13807, South Korea

Jaeyu Park, Dong Keon Yon, Center for Digital Health, Kyung Hee University Medical Center, Seoul 02447, South Korea

Joo Yong Lee, Department of Ophthalmology, Heaan Seoul Eye Center, Seoul 06181, South Korea

Author contributions: Yang JM and Min SH conceived and designed the study with oversight from Kim YJ; Yang JM, Kwak J, Park J, and Yon DK performed the statistical analysis; Yang JM, Kwak J, Min SH, Lee JY, Kim JG, Yoon YH, and Kim YJ collected and interpreted the data; Yang JM and Kwak J drafted the manuscript; Min SH, Choi SU, Park J, Yon DK, Lee JY, Kim JG, Yoon YH, and Kim YJ critically revised the manuscript for important intellectual content; Yoon YH and Kim YJ supervised the project; Kim YJ obtained funding, had full access to all data, and takes responsibility for data integrity and the accuracy of the analysis. All authors approved the final manuscript.

AI contribution statement: The authors take full responsibility and accountability for all content of this manuscript, including any portions for which AI tools were used as assistive technologies. All AI-assisted outputs were carefully reviewed, validated, and approved by the authors. AI tools were not used to generate original scientific data, perform independent scientific analyses, or draw scientific conclusions.

Supported by Korea Drug Development Fund, No. RS-2023-00283544 and No. RS-2024-00405141; National Research Foundation of Korea, No. RS-202400441114; Korean Retina Foundation, 2024 Fund; and Korean ARPA-H Project through the Korea Health Industry Development Institute, No. RS-2025-25455885.

Institutional review board statement: This study was reviewed and approved by the Institutional Review Board of Asan Medical Center, No. 2025-0825.

Informed consent statement: Informed consent was waived due to the retrospective nature of the study.

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.

Data sharing statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.

Corresponding author: Yoon Jeon Kim, MD, PhD, Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, South Korea. yjkim@amc.seoul.kr

Received: April 30, 2026
Revised: June 12, 2026
Accepted: July 28, 2026
Published online: September 15, 2026
Processing time: 124 Days and 16.7 Hours

Abstract

BACKGROUND

Peripheral arterial disease (PAD) and diabetic retinal microvascular complications share systemic vascular pathways, but whether PAD is associated with retinal vessel density reduction and later retinal fluid development in type 2 diabetes mellitus (T2DM) remains unclear.

AIM

To determine whether PAD is associated with retinal microvascular impairment and retinal fluid risk in T2DM.

METHODS

This retrospective cohort included 212 eyes from 203 patients with T2DM without baseline macular edema who underwent complication screening at a tertiary center from December 2016 to February 2021. PAD was defined as ankle-brachial index ≤ 0.9. Optical coherence tomography angiography vessel density was compared by PAD status. Bayesian Cox regression estimated intraretinal fluid and diabetic macular edema (DME) risk, with inverse probability weighting as triangulation.

RESULTS

Among 212 eyes from 203 patients, 25 eyes (11.8%) had PAD. Patients with PAD were older and had lower parafoveal vessel density in the superficial capillary plexus (43.9% vs 46.4%) and deep capillary plexus (46.6% vs 49.7%). PAD was associated with higher intra-retinal fluid (IRF) risk (hazard ratio 5.44; 95% credible interval: 2.11-15.18) and DME risk (hazard ratio 3.54; 95% credible interval: 1.07-11.44), although the wide intervals indicate substantial uncertainty in effect magnitude. Exploratory mediation analysis estimated an indirect proportion of 34% through lower deep capillary plexus vessel density.

CONCLUSION

PAD in T2DM was associated with reduced retinal capillary vessel density and increased incidence of IRF and DME; these observational findings require prospective validation before informing retinal surveillance.

Keywords: Peripheral arterial disease; Type 2 diabetes mellitus; Retinal microvasculature; Intraretinal fluid; Optical coherence tomography angiography

Core Tip: Peripheral arterial disease in type 2 diabetes was associated with lower superficial and deep capillary plexus vessel density on optical coherence tomography angiography and with higher incidence of intraretinal fluid and diabetic macular edema. The association remained positive in the primary Bayesian model and sensitivity analyses, but the small peripheral arterial disease sample and sparse diabetic macular edema events produced substantial uncertainty in effect magnitude. The mediation analysis was exploratory. These findings identify a hypothesis for prospective validation rather than establish a retinal risk-stratification strategy.