Noninvasive Ocular Imaging as a Biomarker for Peripheral Artery Disease


Results from a systematic review highlighted the clinical need for specific biomarkers for PAD and the viability of noninvasive ophthalmic imaging techniques for diagnosis.

Mallika Prem Senthil, PhD, MS | Credit: LinkedIn

Mallika Prem Senthil, PhD, MS

Credit: LinkedIn

Findings from a study assessing the role of ocular imaging as a biomarker in the diagnosis of peripheral artery disease (PAD) are calling attention to the need for a noninvasive ophthalmic imaging technique.

The systematic review included 5 studies using retinal imaging in PAD, highlighting a lack of research about the association between retinal microvascular changes and PAD and suggesting retinal imaging could serve as a quick, noninvasive, and inexpensive imaging biomarker for enhancing risk stratification and guiding response to treatment.1

“PAD is often asymptomatic leading to underdiagnosis and undertreatment. There is a lack of a noninvasive, reliable, and objective biomarker for screening of PAD,” wrote Mallika Prem Senthil, PhD, MS, lecturer at the College of Nursing and Health Sciences at Flinders University in Australia, and colleagues.1

A narrowing of the peripheral arteries that carry blood away from the heart to other parts of the body, PAD is primarily caused by the buildup of fatty plaque in the arteries. According to the US Centers for Disease Control, approximately 6.5 million people > 40 years of age in the United States have PAD. Diagnostic ocular imaging enables noninvasive evaluation of changes in the optic nerve head, nerve fiber layer, and macula, retinal, and choroidal perfusion, which are associated with many neurodegenerative and cardiovascular disorders, highlighting an opportunity for the use of ocular biomarkers in PAD screening.2

To assess the utility of ocular imaging as a biomarker for PAD diagnosis, investigators conducted a literature search of Medline, Embase, Scopus, Cochrane, Latin American and Caribbean Health Sciences Literature, International Standard Randomised Controlled Trial Number registry, and International Clinical Trials Registry Platform for original studies involving patients with any form of PAD. The search was performed on 15 April 2022 and was not limited to any preceding dates. The primary outcome was retinal and choroidal changes in PAD using noninvasive ocular imaging techniques.1

Investigators’ initial search yielded a total of 640 articles, 624 of which were excluded after reviewing titles and abstracts. After applying inclusion criteria to the remaining 16 articles, 11 more were removed. The final review included 5 articles exploring the utility of ocular imaging biomarkers for the diagnosis of PAD.1

Studies dated back to 2020 and included 3 case control studies, 1 cross-sectional study, and 1 prospective study. Of these 5 studies, 2 used retinal color fundus photography, 2 used optical coherence tomography angiography, and 1 used optical coherence tomography as the imaging modality.1

Of the 2 studies involving color fundus photography, the first used a wide-field fundus imaging system with a retinal view of 120° and a deep learning architecture to process retinal color fundus photography images to compare different anatomical structures in patients with PAD (n = 135; mean age, 67.94) and healthy controls (n = 34; mean age, 73 years). Results of this study showed alterations around the optic disc and the temporal vascular arcades can be used to differentiate between patients with PAD and healthy controls.1

The other color fundus photography study included 303 participants with a mean age of 59.5 years and used a nonmydriatic fundus imaging system with a retinal view of 45° to show measures indicative of retinopathy, such as retinal hemorrhages, hard exudates, and microaneurysms, were independently and strongly associated with an increased future risk of PAD.1

Results from both studies using optical coherence tomography angiography showed retinal and choroidal perfusions were reduced in patients with PAD. The first study included 247 patients with cardiovascular disease and found changes in vessel density, vessel perfusion, average vessel length, and/or junction density were linked with aging, hypertension, dyslipidemia, diabetes, chronic renal disease, coronary artery disease, and PAD in 3 × 3 mm optical coherence tomography angiography scans. The second study compared retinal and choriocapillaris perfusion between patients with PAD (n = 52; mean age, 67.94 years) and healthy controls (n = 23; mean age, 69.26 years) and found patients with PAD had a significant reduction in the retinal and choroidal circulation compared to age-matched healthy controls.1

The final study included in the systematic review study used optical coherence tomography to compare the retinal thickness, choroidal thickness, retinal artery diameter, and retinal vein diameter among patients with PAD (n = 35; mean age, 59.4 years) and healthy controls (n = 32; mean age, 55.5 years). Results showed subfoveal choroidal thickness and retinal nerve fiber layer thickness were significantly lower in the PAD group compared to healthy individuals (both P = .03).1

“To conclude, only a few studies have investigated the association between retinal microvascular changes (using OCT or OCTA imaging) and PAD. There is a strong clinical need for more specific biomarkers for PAD because clinical assessment for PAD has a relatively poor predictive value,” investigators wrote.1 “Using a noninvasive ophthalmic imaging technique in PAD would significantly improve the rate of diagnosis without putting the patients at risk of complications. Early detection of PAD and subsequent treatment may have the potential to enhance quality of life and improve clinical outcomes for patients with PAD.”


  1. Prem Senthil M, Kurban C, Thuy Nguyen N, et al. Role of noninvasive ocular imaging as a biomarker in peripheral artery disease: A systematic review. Vascular Medicine. 2023;0(0). doi:10.1177/1358863X231210866
  2. US Centers for Disease Control and Prevention. Peripheral Arterial Disease (PAD). Heart Disease. December 19, 2022. Accessed December 7, 2023.
Recent Videos
1 KOL is featured in this Insights series.
Charles C. Wykoff, MD, PhD: Interim Analysis on Ixo-Vec Gene Therapy for nAMD | Image Credit: Retina Consultants of Texas
Sunir J. Garg, MD: Pegcetacoplan Preserves Visual Function on Microperimetry | Image Credit: Wills Eye Hospital
Edward H. Wood, MD: Pharmacodynamics of Subretinal RGX-314 for Wet AMD | Image Credit: Austin Retina Associates
Dilsher Dhoot, MD: OTX-TKI for NPDR in Interim Phase 1 HELIOS Results  | Image Credit: LinkedIn
Katherine Talcott, MD: Baseline EZ Integrity Features Predict GA Progression | Image Credit: LinkedIn
Veeral Sheth, MD: Assessment of EYP-1901 Supplemental Injection Use in Wet AMD | Image Credit: University Retina
Discussing Post-Hoc Data on Ruxolitinib for Nonsegmental Vitiligo, with David Rosmarin, MD
A panel of 3 experts on dry eye
1 KOL is featured in this series.
© 2024 MJH Life Sciences

All rights reserved.