Retinal Fundus Imaging and OCT Imaging for Ocular Detection of ATTR-CM

A Multicenter Pilot Study to Investigate Ocular Involvement and the Potential of Ocular Imaging for Non-invasive Screening for Transthyretin Amyloid Cardiomyopathy (ATTR-CM)

This multicenter pilot study will enroll adult participants with a confirmed clinical diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM) and heart failure (HF) controls with documentation within the past 2 years that either excludes ATTR-CM or indicates a low probability of ATTR-CM. Ocular imaging and other study data will be collected to assess the feasibility of developing and preliminarily evaluating a machine learning model to discriminate ATTR-CM cases from HF controls without ATTR-CM.

A participant who does not complete the study within 90 days from enrollment will be discontinued from the study. A participant may be discontinued from the study at any time at the discretion of the investigator for behavioral or compliance reasons. A participant may withdraw from the study at any time at the participant's own request for any reason (or without providing any reason) without any implication on participant's rights.

Inclusion Criteria:

• 1. Participant must be 18 years and older at the time of signing the informed consent form.
• 2. Participants with either of the following:
• - Positive ATTR-CM cases: Participants with a clinical diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM) with amyloid deposits in cardiac or non-cardiac tissue confirmed by Congo Red (or equivalent) staining, or DPD-Tc, PYP-Tc, or HMDP-Tc scintigraphy with Grade 2 or 3 cardiac uptake in the absence of abnormal light chains ratio.
• - Control population: Participants with a clinical diagnosis of guideline-directed medical therapy-directed heart failure (HF) and either:
• a) Subgroup A: Definitively excluded ATTR-CM amyloidosis: negative cardiac or non-cardiac tissue biopsy for amyloid, or negative technetium scintigraphy within the past 2 years.
• b) Subgroup B: Low probability of ATTR-CM amyloidosis, not definitively excluded: absence of amyloid-suggestive features on echocardiography (ECHO), electrocardiography (ECG), or cardiac magnetic resonance imaging (MRI) within the past 2 years, with documented clinical assessment indicating HF etiology unlikely attributable to amyloidosis; no amyloid-specific testing (technetium scintigraphy or biopsy) performed.
• 3. Participant or legally authorized representative (LAR) must sign the informed consent form.

Exclusion Criteria:

• 1. Any known eye condition that may preclude clear imaging of the retina.
• 2. Any known history of amyloid light-chain (AL) amyloidosis.
• 3. Any ocular surgery that, in the opinion of the investigator, makes participation in the study undesirable.
• 4. Any medical condition that, in the opinion of the investigator, makes participation in the study undesirable, for example, if the participant is critically unwell or requires ongoing emergency treatment.
• 5. Involvement in the planning and/or conduct of the study.
• 6. In the opinion of the investigator, the participant is unlikely to comply with study procedures, restrictions, and requirements.
• 7. Previous enrollment in the present study.