Imaging the retina for early diagnosis in Alzheimer's disease

Alzheimer*s disease (AD) is by far the most important cause of dementia. The
diagnosis of AD is based on clinical criteria supported by either magnetic
resonance imaging (MRI), positron emission tomography (PET) or cerebrospinal
fluid (CSF) analysis. These ancillary investigations are expensive and/or
invasive. What is needed is a non-invasive, cheap and fast, patient friendly
method, suitable for use in an outpatient setting. The eye is a direct
protrusion from the brain and the retina has many structural similarities with
the brain. The retina is easily accessible for ophthalmological examination. As
such, the retina can be of interest as a *window to the brain* and offers a
potential new diagnostic method for early diagnosis of AD and/or follow-up of
possibly therapeutic agents in the future.

This proof-of-concept study aims to non-invasively detect amyloid-beta (Aβ)-
plaques in the retina of AD patients using a Heidelberg Spectralis scanner with
Curcumin as labeling fluorophore. The retinal Aβ-plaques will be related to
currently used AD biomarkers such as hippocampal atrophy on MRI, Aβ1-42-level
in CSF and amyloid-PET imaging.

Proof of concept diagnostic observational clinical cross sectional study.
During the first visit we will conduct a thorough baseline ophthalmological
examination including baseline cfSLO, which will take around 60-80 minutes.
During the 10 days prior to the third visit patients will take an oral daily
dose of Curcumin followed by examination with the Spectralis scanner. This will
take around 30 minutes.

Patients will have three extra site visits, next to the regular visits for
patient care in the VUmc Alzheimer Center. The first to obtain baseline
ophthalmological characteristics, the second for short medical check and
bloodsampling and the third to perform Spectralis scanning after 10 days of
Longvida administration prior to this visit. Longvida dose levels up to 4000 mg
have been given to humans without safety concerns and without side effects. For
standard ophthalmological examination and to improve the quality of the optical
coherence tomography (OCT) and Spectralis images, pupil dilatation is necessary
with a topical mydriatic (Tropicamide). Pupil dilatation may cause a modest
amount of transient photophobia and blurred vision in some participants,
lasting several hours. This may interfere with car driving, so patients are
advised not to drive themselves. Adverse ocular or systemic side effects of
Tropicamide are very rare. Baseline ophthalmological investigations include
OCT, Frequency Doubling Technology (FDT) and the Heidelberg Retinal Tomograph
II (HRTII). Both these and the Heidelberg Spectralis scanner are non-invasive
optical eye examinations in which light is used to examine the posterior part
of the eye. The used wavelength and the overall energy level of the light is
well below the safety margins and is harmless and without risks.