Retinal Imaging Findings in PSEN-1-associated Early Onset Familial Alzheimer’s Disease before Onset of Cognitive Symptoms

Abstract

Purpose : Optical coherence tomography (OCT) and vascular tortuosity surfaced as a biomarker of interest in non-familial Alzheimer's disease (AD) patients as it provides a non-invasive mechanism capable of analyzing central nervous system tissues. For familial cases of AD, such as those caused by PSEN-1 mutations (presenilin), it is possible to identify unique early ophthalmologic biomarkers of disease while eliminating many age-related confounding variables. We analyzed OCT imaging and color fundus photos of familial AD patients in an attempt to elucidate early biomarkers of disease.

Methods : Ten patients with confirmed PNES-1 mutations and ten controls, all from a patient cohort from South America with a family history of said mutation, underwent retinal imaging. OCT thickness map was generated using the conventional Early Treatment Diabetic Retinopathy Study (ETDRS) grid.
Color fundus photos were analyzed with MATLAB. Retinal arteries and veins were segmented by local thresholding via Niblack’s method,. Fractal dimension of the whole vascular network was calculated using the box-counting method. Tortuosity index in each vessel segment was defined as arclength divided by chordlength.

Results : OCT- There was a generalized decrease in thickness of the whole retina as well as individual layers in the PSEN-1 carrier group, in comparison to controls. The largest % difference in thickness was seen in the photoreceptor layer. The most statistically significant difference in thickness was seen in the inner and outer nuclear layers (INL, ONL). The interaction between age and PSEN mutation contributing to retinal thickness was non-significant in the outer nuclear layer.
Color fundus photo- There was no statistical difference between number of arterial/venous branch points, arterial/venous tortuosity, nor fractal dimension between the control and PSEN-1 carrier groups.

Conclusions : Unlike earlier studies reporting significant reduction in peripapillary RNFL thickness in non-familial AD, our familial AD cohort showed statistically significant reduction in the INL and ONL. Degree of thinning was age-independent on analysis of covariance, which may suggest pathologic changes in the retina that happens at a younger age than the age range of our cohort (28-55). Retinal imaging can introduce new biomarkers as well as further the understanding of retinal changes seen in AD.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.