Assessment of foveal avascular zone and retinal microvascular changes in patients with Alzheimer disease based on OCTA

Objective  To evaluate changes in the morphological characteristics of the foveal avascular zone (FAZ) and retinal microvascular features in patients with Alzheimer disease (AD) using optical coherence tomography angiography (OCTA), and to analyze the correlations between FAZ morphology and retinal microvascular parameters.

Methods  A multi-centered cross-sectional study was conducted. Fifty-five patients (110 eyes) with AD who were admitted to the First Affiliated Hospital of Wenzhou Medical University and West China Hospital of Sichuan University from December 2020 to April 2023, and 53 healthy adults (106 eyes) who were admitted to West China Hospital of Sichuan University for physical examination, were included as the control group. All participants underwent Mini-Mental State Examination (MMSE) assessment. OCTA was used to obtain FAZ-related parameters and retinal microvascular characteristics in the deep vascular complex (DVC) and superficial vascular complex (SVC). A generalized estimation equation was used to compare the differences in OCTA-derived characteristic parameters between the two groups, and Pearson correlation analysis was performed to assess the associations of FAZ morphological features, texture features, and retinal microvascular parameters with MMSE scores. This study was in accordance with the Declaration of Helsinki. The study protocol was approved by the Biomedical Research Ethics Committee and the Human Research Committee of the First Affiliated Hospital of Wenzhou Medical University (No.2023130) and West China Hospital of Sichuan University (No. 2020104). Written informed consent was obtained from all participants or their legal guardians before enrollment.

Results  In the whole-region FAZ analysis, there were statistically significant differences in the circularity and convexity in both the DVC and SVC layers between the AD and control groups (all P<0.01). For FAZ texture features, there were statistically significant differences in contrast and entropy in the DVC and SVC layers between the two groups (all P<0.05). For FAZ microvascular features, there were statistically significant differences in vessel fractal dimension in the DVC layer, as well as vessel area density, vessel length density, and vessel fractal dimension in the SVC layer between the AD and control groups (all P<0.05). Among the four-region FAZ morphological characteristics, there were statistically significant differences in FAZ area and convexity in the inferior and nasal regions of the DVC layer, as well as in FAZ area in the inferior and nasal regions of the SVC layer between the two groups (all P<0.05). Among the FAZ texture characteristics, there were statistically significant differences in contrast, energy, entropy of inferior, nasal, superior, temporal DVC and superior DVC correlation between the two groups (all P<0.05); there were statistically significant differences in temporal SVC correlation and energy and entropy of inferior, nasal, and superior SVC between the two groups (all P<0.05). Among the microvascular characteristics of FAZ, there were statistically significant differences in the vessel area density and vessel length density in inferior, nasal, superior, and temporal DVC (all P<0.05); there were statistically significant differences in the vessel area density in inferior, nasal, superior, and temporal SVC (all P<0.05). In AD patients, the FAZ area in the DVC layer and SVC layer was negatively correlated with the vascular fractal dimension ( r=-0.230, -0.210; both P<0.05), the entropy of the DVC layer was positively correlated with the vascular area density ( r=0.190, P<0.05), the FAZ contrast in the DVC layer was positively correlated with the vessel area density, vessel length density, and vessel fractal dimension ( r=0.310, 0.260, 0.220; all P<0.05). MMSE scores in patients with AD were positively correlated with circularity in both the DVC and SVC layers ( r=0.294, 0.245; both P < 0.01), negatively correlated with contrast in both layers ( r=-0.126, -0.148; both P<0.05), and positively correlated with vessel area density, vessel length density, and vessel fractal dimension in both layers (DVC: r=0.084, 0.098, 0.125; all P<0.05; SVC: r=0.106, 0.109, 0.105; all P<0.05).

Conclusions  OCTA can directly reveal the changes of FAZ morphology and retinal microvascular in AD patients, which are highly correlated with cognitive function and provide potential biomarkers for the early detection of AD.