Retinal Optical Coherence Tomography Angiography as a Non-Invasive Marker of Coronary Microvascular Dysfunction in Patients with Ischemia with Non-Obstructive Coronary Arteries (INOCA)

Background: Ischemia with non-obstructive coronary arteries (INOCA) is frequently associated with coronary microvascular dysfunction (CMD), which contributes to persistent myocardial ischaemia despite the absence of flow-limiting epicardial coronary stenosis. Optical coherence tomography angiography (OCTA) permits non-invasive quantitative assessment of the retinal microcirculation and may provide a surrogate marker of systemic microvascular dysfunction. Objective: To evaluate the association between retinal microvascular alterations quantified using OCTA and CMD assessed using coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) in patients with INOCA. Methods: This prospective observational study included 69 adults with INOCA who underwent invasive coronary physiological assessment and retinal OCTA. CMD was defined using thermodilution-derived CFR <2.5 and/or IMR ≥25 units. Retinal vessel density, inner retinal perfusion density, deep capillary plexus vessel density, and foveal avascular zone parameters were analysed. Results: CMD was present in 38 patients (55.1%). Patients with CMD had significantly lower CFR (2.10 ± 0.40 vs 3.23 ± 0.50; p<0.001) and higher IMR (31.4 ± 8.0 vs 17.0 ± 3.3 units; p<0.001). Superficial retinal vessel density (21.05 ± 0.49 vs 21.66 ± 0.46; p<0.001) and inner retinal perfusion density (39.38 ± 1.22% vs 40.80 ± 1.18%; p<0.001) were significantly lower in CMD. Both parameters correlated positively with CFR and inversely with IMR. After adjustment for age, sex, body mass index, hypertension, and diabetes mellitus, lower superficial vessel density (adjusted OR 4.34, 95% CI 2.07–9.10) and lower inner retinal perfusion density (adjusted OR 3.40, 95% CI 1.78–6.51) remained independently associated with CMD. Conclusion: Retinal OCTA-derived superficial vessel density and inner retinal perfusion density were significantly associated with invasively defined CMD in patients with INOCA and may represent promising non-invasive markers of coronary microvascular impairment.