Retinal Biomarkers of Alzheimer’s Disease

Abstract

Purpose : Retinas of people with Alzheimer's Disease (AD) may experience neuroinflammatory processes, similar to brain. Inflammatory injury may cause atrophy of axonal projections and/or extracellular deposits. Our objective is to determine whether nerve fiber layer (NFL) thickness or peripheral (non-macular) drusen deposits may serve as non-invasive, inexpensive biomarkers to help diagnose AD.

Methods : NCT01937221 enrolled three age-matched groups: 15 patients with mild cognitive impairment (MCI)/prodromal AD, 15 patients with moderate AD, 17 cognitively normal adults. Assignment to group was made by consensus diagnosis of a neurologist and neuropsychologist. We excluded eyes with major eye diseases or diagnoses that may cause NFL thinning (e.g. normal tension glaucoma). Study participants underwent examination, spectral domain optical coherence tomography (SD-OCT), wide-field fundus color and autofluorescence (AF) photography and stereo disc photography. Location-specific NFL thicknesses were measured using Duke Optical Coherence Tomography Retinal Analysis Program (DOCTRAP) software. Mean NFL thicknesses are compared with generalized estimating equations (GEE). Peripheral drusen were graded by retinal specialists masked to group assignment. Proportion of participants with evident drusen was compared by chi-square test. Participants are returning for 1-year follow-up exams.

Results : Participants in the AD group were more likely to have peripheral drusen visible on color or AF photography (66.7%), compared to participants in MCI (35.7%) or control (37.5%) group (p=0.06). When drusen was present, it was bilateral in 16 of 17 subjects with two eligible eyes. Preliminary analysis from macular OCT did not reveal significant group differences in macular NFL thickness. Ongoing work will address artifact (e.g., ERMs) and evaluate NFL/GCL thickness around the optic nerve. We will present longitudinal analyses to address stability/progression of biomarkers.

Conclusions : Compared to age-matched controls or subjects with MCI, patients with moderate AD had a higher burden of peripheral retinal drusen deposits. Further analysis will pinpoint location of deposits within retinal layers and evaluate other means of quantification. Our preliminary negative findings with regard to macular NFL thickness controvert a previous group’s finding of thinner NFL in persons with moderate-to-severe AD. We will present ongoing analysis on other measures of retinal thickness.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.