Drusen in the Peripheral Retina of the Alzheimer’s Eye

Abstract

Purpose : Recent work on Alzheimer's disease (AD) diagnosis has focused on neuroimaging, in particular CT, MRI and PET; however, neuroimaging is expensive, sometimes invasive and not available to all patients. Ocular biomarkers could provide an alternative way to diagnose AD, and may be more accessible than neuroimaging. Based on previous studies suggesting that peripheral drusen may be useful as an AD biomarker, we tested the hypothesis that peripheral hard drusen would be increased in AD patients compared to controls using post-mortem eye tissues.

Methods : We assessed the histological evidence for drusen in postmortem eye tissues obtained from donors with a primary or secondary pathological diagnosis of AD. Retina from normal donors were processed and categorized into younger (≤ 55 years old) and older (>55 years old) groups. After fixation and dissection, 6-mm punches of RPE/choroid were taken in macular (centered on fovea), superior, inferior, and temporal retinal regions. In order to identify drusen, Oil Red - a stain that binds to neutral lipids - was used. Hard drusen were measured, counted and grouped into two size categories: small (≤ 63µm) and intermediate (63-125µm). The number of hard drusen was normalized to the surface area of the punch. Statistical analyses were performed using SPSS.

Results : There was a significant increase in the total number of macular hard drusen and peripheral hard drusen in older, compared to younger, normal eyes, as expected (p<0.05). However, significance was not reached for small hard drusen in AD eyes compared to older normal eyes. Interestingly, intermediate hard drusen were more commonly found in the temporal region of AD eyes compared to older normal eyes (p<0.05). Among the brain and eye tissues from AD donors, there was a strong relationship between cerebral amyloid angiopathy (CAA) score and number of intermediate hard drusen in the temporal region of the retina (R2=0.6, p<0.05).

Conclusions : Results suggest that peripheral drusen may be useful for further biomarker studies assessing the eye of AD patients, as the number of intermediate hard drusen in the temporal peripheral retina is increased compared to controls, and is positively correlated with CAA severity in corresponding AD brain tissue. Thus, non-invasive fundus imaging of temporal intermediate drusen may have biomarker potential for AD detection and/or progression and is worthy of further investigation.

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