Ophthalmological Microvascular Changes in ANOCA/INOCA Disease and Ophthalmological Methods to Detect Them—A Systematic Review

TL;DR

This review explores how eye microvascular changes can help detect heart disease subtypes like ANOCA/INOCA using non-invasive imaging techniques.

Contribution

The paper systematically reviews ophthalmological methods for detecting microvascular changes in ANOCA/INOCA patients, highlighting their potential as non-invasive diagnostic tools.

Findings

Optical coherence tomography angiography was the most commonly used method to assess microvascular changes.

Retinal and conjunctival microvascular alterations may reflect systemic microcirculatory issues in ANOCA/INOCA patients.

Ophthalmological imaging could serve as a non-invasive tool for detecting CMD in these patients.

Abstract

Background/Objectives: Coronary artery disease (CAD) remains one of the leading cardiovascular diseases worldwide. While obstructive CAD is well characterized and managed, identification of patients with non-obstructive CAD (NOCAD) remains challenging. Unlike the coronary vasculature, the eye’s microcirculation can be easily and non-invasively assessed. Therefore, this systematic review summarized the ophthalmological diagnostic methods used to assess microvascular alterations associated with coronary microvascular dysfunction (CMD), angina with non-obstructive coronary arteries (ANOCA), or ischemia with non-obstructive coronary arteries (INOCA). Methods: According to PRISMA guidelines, PubMed/MEDLINE and Embase databases were screened by two independent reviewers from inception to 25 November 2025. Original articles that examined ophthalmological microvascular changes by any method in adults with CMD or its subtypes were included. The quality of the studies was assessed using the JBI Critical Appraisal Checklist. Results: Of 101 identified articles, nine studies met the inclusion criteria, comprising 1894 patients. Optical coherence tomography angiography was the most frequently used imaging modality, followed by optical coherence tomography, slit-lamp smartphone imaging, and fundus photography. Five investigations employed blinded image analysis, three did not, and one study used it partially. Four studies used semi-automated measurements, four employed fully automated methods, and one study applied manual and automated measurements for different parameters. Conclusions: Despite a limited number of studies, retinal and conjunctival microvascular alterations helped differentiate CAD subtypes and may reflect systemic microcirculatory impairment among patients with ANOCA/INOCA. Ophthalmological imaging techniques have the potential to serve as non-invasive tools for detecting microvascular alterations associated with CMD in ANOCA and INOCA patients. PROSPERO Registration Number: CRD420251239875

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