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Eyes on amyloidosis: microvascular retinal dysfunction in cardiac amyloidosis
Emanuel Zampiccoli1, Jens Barthelmes1, Leonie Kreysing1
1Department of Cardiology, University Hospital Zurich, University of Zurich, Raemistrasse 100, Zurich, 8091, Switzerland.
Insights
Retinal vascular dysfunction, measured by flicker-induced arterial dilatation (FIDa), is significantly impaired in cardiac amyloidosis (CA) patients. This impairment correlates with disease severity markers and suggests FIDa as a potential therapeutic target for CA.
Area of Science:
- Cardiology
- Ophthalmology
- Vascular Biology
Background:
- Cardiac amyloidosis (CA) significantly worsens prognosis, characterized by amyloid deposits causing heart failure and microvascular disease.
- The role of vascular dysfunction in CA pathophysiology is not fully understood, despite its association with cardiovascular risk and heart failure severity.
- Vascular function represents a potential therapeutic target in CA, necessitating further investigation into its specific manifestations.
Purpose of the Study:
- To investigate retinal vascular function, including flow-mediated dilatation (FMD) and pulse-wave analysis and velocity (PWA/PWV), in patients with CA.
- To assess flicker-induced arterial dilatation (FIDa) using dynamic retinal vessel analysis in CA patients.
- To explore the association between retinal vascular function and prognostic biomarkers in CA.
Main Methods:
- A cross-sectional, observational study included 33 CA patients (14 AL, 19 ATTR) and 70 healthy controls.
- Measurements included FMD, PWA/PWV, and FIDa assessed via dynamic retinal vessel analysis.
- Entropy balancing propensity score analysis (inverse probability weighting) was used to balance confounders.
Main Results:
- Flicker-induced arterial dilatation (FIDa) was significantly reduced in CA patients compared to controls (1.52 ± 1.73% vs. 3.09 ± 1.96%, P < 0.001).
- Pulse-wave velocity (PWV) was increased in CA patients (8.74 ± 2.34 m/s vs. 7.49 ± 1.65 m/s, P = 0.018), while FMD showed no significant difference.
- Reduced FIDa was significantly associated with poorer prognostic biomarkers: lower estimated glomerular filtration rate, higher log-scaled troponin T, and higher N-terminal pro-B-type natriuretic peptide.
Conclusions:
- Retinal vascular function, specifically FIDa, is impaired in patients with cardiac amyloidosis.
- This impairment is significantly associated with cardiac and renal biomarkers, reflecting CA severity.
- Retinal vascular function may serve as a potential therapeutic target for managing amyloidosis.
Aims:
Cardiac involvement in systemic amyloidosis is a marker of particularly poor prognosis. Cardiac amyloidosis (CA) is characterized by extracellular amyloid deposits inducing heart failure and symptoms of cardiac microvascular disease. While amyloid deposition is most common in the myocardium but also seen in pericardium and endocardium, atria, and vasculature, the role of (micro-)vascular dysfunction in CA pathophysiology remains still elusive. Because vascular function is associated with cardiovascular risk and severity of heart failure and represents a potential therapeutic target in CA, the present study investigated retinal vascular function, flow-mediated dilatation (FMD), and pulse-wave analysis and velocity (PWA/PWV) in patients with CA.
Methods And Results:
Flicker-induced arterial dilatation (FIDa) was measured using dynamic retinal vessel analysis additionally to FMD and PWA/PWV. Thirty-three patients with CA [age 67 years [interquartile range, IQR, 62, 74], 14 with amyloid light-chain (AL) and 19 with transthyretin (ATTR) amyloidosis] were prospectively included in this cross-sectional, observational study and 70 healthy individuals (age 53 years [IQR 39, 67]) served as control. Potential confounders were balanced using entropy balancing propensity score analysis [inverse probability weighting (IPW)]. FIDa was reduced in CA patients (1.52 ± 1.73% vs. 3.09 ± 1.96%, P < 0.001, after IPW). While PWV was increased (8.74 ± 2.34 m/s vs. 7.49 ± 1.65 m/s, P = 0.018, after IPW), no difference in FMD was observed. FIDa was significantly associated with prognostic biomarkers of CA [estimated glomerular filtration rate (r = 0.33; P < 0.001), log-scaled troponin T (r = -0.49; P < 0.001), and N-terminal pro-B-type natriuretic peptide (r = -0.51; P < 0.001)].
Conclusions:
Retinal vascular function is impaired, associated with cardiac and renal biomarkers of CA severity, and may represent a potential therapeutic target in patients with amyloidosis.
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