Retinal Metabolic Imaging of Alzheimer Patient

Evaluation of Beta-amyloid Plaques of the Retina Using Metabolic Hyperspectral Retinal Camera (MHRC) in Alzheimer's Patients - Toronto Study Arm

This research project concerns the evaluation of the Metabolic Hyperspectral Retinal Camera (MHRC), a novel medical instrument from Optina Diagnostics, for the detection of beta-amyloid plaques, a hallmark of Alzheimer's disease (AD), in the retina. The experimental device, produces multiple images of the retina when subjected to light in very specific colors (90-100 specific colors typically) and may be used to identify specific biomarkers based on their unique spectral signature. The retina is an extension of the brain and is the only optically accessible nervous tissue. The MHRC could represent a simple and non-invasive tool to facilitate the diagnosis of AD.

Study Overview

• Status: Completed
• Conditions: Alzheimer Disease
• Intervention / Treatment: Device: MHRC

Detailed Description

Alzheimer's disease (AD), a neurodegenerative disorder characterized by cognitive impairment and a suspected dementia syndrome, is the most common type of dementia (>50% of all cases), affecting millions worldwide, with no cure available at this time. Definite AD diagnosis currently relies on the post-mortem observation of the hallmarks β-amyloid peptides (Aβ) extracellular aggregates, Aβ plaques, and protein tau intracellular twisted strands (neurofibrillary tangles, NFTs). Earlier diagnosis could dramatically transform the design and execution of clinical trials to test new treatments. The eye offers a natural window to the brain as the retina, the light sensitive layer lining the interior of the eye is an extension of the brain. The presence of Aβ plaques in the retina of AD mice models and humans was recently reported opening the possibility of detecting this AD hallmark though a simple non-invasive eye scan. The proposed research aims to explore this avenue with the development of a spectrally-resolved optical retinal imaging platform to detect Aβ plaques in the retina of AD subjects and validate the method against brain Aβ plaques seen on amyloid PET imaging. The novel imaging platform is expected to help aid the early detection of AD and assist in monitoring efficacy of possible future therapeutic agents that target relevant molecular pathways.

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects with Alzheimer's disease

   • Meet criteria for probable, possible Alzheimer's disease by McKhann criteria (McKhann et al. 2011)
   • Mini-Mental State Examination score between 20 and 27 (inclusive)
   • Vascular load scale ≤ 4 (Hachinski Ischaemia Score)
   • Sufficient degree of cooperation to undergo all examinations
   • Availability of a reliable responsible study partner to accompany the patient to the appointments

2. Subjects with Mild Cognitive Impairment

   • Meet criteria for amnestic single or multi domain Mild Cognitive Impairment (without crossing the threshold for dementia)
   • No signs of systemic, neurologic or psychiatric disorders that can cause cognitive deficits
   • Scores on cognitive tests: 1 to 1.5 standard deviation below the mean of their age and education matched peers
   • Diagnosis that follows Albert criteria (Albert et al. 2011)

3. Healthy control subjects

   • No clinical signs of dementia
   • Telephone Mini-Mental State Examination score ≥ 25 or
   • MoCA ≥ 26
   • Behavioural Neurology Assessment-R (BNA-R; Annex IX; within limits on all sub tests)

Exclusion Criteria:

• Presence of one or more contraindications (PET and/or MRI)
• Presence of glaucoma or retinopathy (diabetic, macular degeneration)
• Pupil dilation inadequate or contraindicated
• Deficient visual fixation
• Refractive error outside the range -9 to +9
• Impossibility of obtaining satisfactory, quality images with MHRC

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MHRC camera; Subjects will undergo a retina imaging session with the MHRC camera.	Device: MHRC; Evaluate the feasibility of detection of beta-amyloid plaques by using their spectral signature in autofluorescence or reflectance.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Retinal beta-amyloid detection	Presence of absence of beta-amyloid plaques in the retina	Within 21 days following clinical characterization completion

Collaborators and Investigators

• Sponsor: Optina Diagnostics Inc.
• Collaborators: Sunnybrook Health Sciences Centre; McGill University

Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2017
• Primary Completion (Actual): March 12, 2020
• Study Completion (Actual): March 12, 2020

Study Registration Dates

• First Submitted: January 29, 2018
• First Submitted That Met QC Criteria: January 29, 2018
• First Posted (Actual): February 5, 2018

Study Record Updates

• Last Update Posted (Actual): March 28, 2023
• Last Update Submitted That Met QC Criteria: March 24, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: 071317

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No