Assessing retinal vascular biomarkers for Alzheimer’s disease using ultra-widefield imaging (UWFI)

Abstract

Purpose : Pathological changes in the eye have been reported in a range of neurodegenerative diseases including changes in retinal vascular parameters (RVPs). The purpose of this study was to assess whether there are measurable RVP changes associated with Alzheimer`s disease (AD) using UWFI and whether any progression related changes can be detected during a 2 year period.

Methods : UWFiI were acquired of 20 healthy controls (HC; (MMSE>28) and 13 participants with AD (MMSE<26) using an OPTOS TX 200 scanning laser ophthalmoscope at baseline (BL) and after a two-year follow-up (FU). The study had full local Ethical Committee approval. Images were analysed using previously developed segmentation and analysis algorithms for UWFI to measure several different RVPs including arterial and venular branching, vessel width gradient (WG), fractal dimensions (FD) of the vascular network patterns and vessel tortuosity. Analysis was carried out either on the whole image or in a circular zone (Zone C) centred on the optic disc (OD) stretching from 0.5 ODDs to 2 ODDs from the OD boundary. The image and zone was further divided into four quadrants centred on the OD. Statistical analysis was carried out in GraphPad Prism (version 7.02, 2016) using a paired and unpaired t-test where appropriate; here results with p<0.05 were reported.

Results : In total, 78 images were included in the analysis (46 HC and 32 AD). There was no significant difference in age between HC and AD (77.7±7.2 vs. 71.3±10.2; p>0.1). At BL there was decreased arterial FD (HC=1.3±0.02; AD=1.2±0.02; P<0.05) and increased arterial WG (HC=3.86x10^-3±1.39x10^-3; AD=8.43x10^-3±1.72x10^-3; p<0.05) at the inferior-nasal quadrant on the entire image as well as in Zone C. There was an increase in venular WG in superior-nasal quadrant (HC=4.55x10^-3±6.03x10^-4; AD=9.93x10^-3±1.77x10^-3; p<0.01) and also when all quadrant were considered together (HC=5.85x10^-3±3.23x10^-4; AD=8.01x10^-3±7.08x10^-4; p<0.01) on the entire image as well as in Zone C. From BL to FU our analysis could not detect progression in any of the RVPs.

Conclusions : Our preliminary data suggests that retinal vascular biomarkers measured on UWFI can distinguish between HC and AD at baseline but might not be sensitive enough to detect progression during a 2 year period. Larger participant numbers and longer FU period might be needed to detect progression of RVPs.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.