Retinal microvascular alterations reflect systemic hypoxia burden in stable chronic obstructive pulmonary disease: an optical coherence tomography angiography study

Abstract

Background
Chronic obstructive pulmonary disease (COPD) is increasingly recognized as a systemic disorder associated with endothelial dysfunction, chronic hypoxemia, and widespread microvascular impairment. Optical coherence tomography angiography (OCTA) provides a rapid, non-invasive quantitative assessment of retinal microvascular architecture and may offer insights into systemic microvascular alterations.


Objective
To evaluate retinal macular microvascular changes in patients with stable COPD using OCTA and investigate their associations with disease severity and systemic hypoxia.


Methods
In this hospital-based case–control study, 60 patients with stable COPD diagnosed according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria and 60 age- and sex-matched healthy controls underwent OCTA imaging using the RTVue XR Avanti system. Quantitative measurements included the foveal avascular zone (FAZ) area and vessel density within the superficial capillary plexus, deep capillary plexus, and choriocapillaris. Clinical characteristics, pulmonary function, arterial blood gas parameters, and smoking exposure were recorded. Multivariable linear regression analysis was performed to identify independent predictors of FAZ enlargement.


Results
Compared with healthy controls, patients with stable COPD exhibited significantly larger FAZ areas and reduced parafoveal vessel density across retinal vascular plexuses. Retinal microvascular impairment progressively worsened with increasing GOLD severity. FAZ enlargement was significantly associated with lower forced expiratory volume in one second (FEV₁), greater hypoxemia, higher dyspnea grade, increased smoking exposure, and more frequent exacerbations. After adjustment for age, body mass index, smoking exposure, and FEV₁ (% predicted), lower arterial oxygen tension (PaO₂) remained independently associated with greater FAZ area, whereas smoking exposure was not independently associated with FAZ enlargement.


Conclusion
OCTA-derived retinal microvascular parameters were significantly associated with systemic hypoxemia and COPD severity, supporting their potential role as complementary, non-invasive biomarkers for assessing systemic microvascular involvement in stable COPD. These findings highlight the complementary value of OCTA in evaluating systemic microvascular alterations beyond conventional pulmonary function assessment and warrant confirmation in prospective longitudinal studies.