Retinal vascular changes in typical Alzheimer’s disease and posterior cortical atrophy using ultra-widefield retinal image analysis

Abstract

Purpose : Our previous studies showed that AMD-like pathologies have a higher prevalence in the peripheral retina in the eyes of patients with typical Alzheimer’s Disease (tAD) and posterior cortical atrophy (PCA) compared to cognitively normal controls (Csincsik et al. 2021). Whether differences exist in retinal vascular parameters (RVPs) has yet to be examined in this cohort.

Methods : Ultra-widefield retinal images (UWFI) were acquired from 24 people with tAD (MMSE<20), 25 with PCA (MMSE<24), and 69 controls (MMSE>28) using an OPTOS P200Tx scanning laser ophthalmoscope. Images were analyzed using VAMPIRE-UWF (Vascular Assessment and Measurement Platform for Images of the Retina) to measure RVPs, including vessel width gradient (WG), branching complexity (fractal dimension; FD), and vessel tortuosity. Analysis was performed within a standardized region of interest (SRI) determined from the entire cohort. The SRI was divided into four retinal quadrants centred on the optic disc. Generalized estimating equations were used to compare groups with sex and age as covariates. The study had full local Ethical Committee approval.

Results : There was no evidence of significant differences in age, sex, and disease duration between the groups. There was an increased rate of global venular thinning in tAD (WGβ: -0.660±0.24; p=0.006) and in the inferior temporal quadrant in PCA compared to controls (WGβ: -0.869±0.34; p=0.011). There was a decrease in global arterial tortuosity in PCA compared to controls (TORTaβ: -0.162±0.071; p=0.022) and a trend in tAD (TORTaβ: -0.134±0.071, p=0.059). Midperipheral vascular complexity was decreased in tAD (FDβ: -0.029±0.012; p=0.015).

Conclusions : Analysing RVPs on UWFI may distinguish between cognitively normal individuals and tAD and PCA. These vascular changes may contribute to the peripheral retinal changes reported in the same cohort (Csincsik et al. 2021). Larger participant numbers and follow-up studies will be needed to validate these observations to determine if RVPs can translate to ocular biomarkers for dementia progression and endotyping. Given the small but discernible differences between tAD and PCA, our results highlight the importance of including well-characterized cases in dementia studies for developing relevant and reliable ocular biomarkers.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.