SEARCHCROSS-SECTIONALophthalmology, cornea

cross-sectional·ophthalmology, cornea, neurology, cardiology, clinical trial·PMC10267010

Corneal confocal microscopy identifies corneal nerve loss and increased Langerhans cells in presymptomatic carriers and patients with hereditary transthyretin amyloidosis

Journal of Neurology · 13 authors, 8 centres

AI SUMMARY

FIDELITY 100%

POPULATION20 patients with hereditary transthyretin amyloidosis (ATTRv), 5 presymptomatic carriers, and 20 age- and sex-matched healthy controls

INTERVENTIONCorneal confocal microscopy assessment of corneal nerve fibre density, nerve fibre length, nerve branch density, and cell infiltrates

COMPARISONHealthy controls

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AGENT 01 · STRUCTURED SUMMARY

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TL;DR

This cross-sectional study used corneal confocal microscopy to show that patients with hereditary transthyretin amyloidosis and presymptomatic carriers have significantly reduced corneal nerve fibre density compared to healthy controls. Patients also exhibited increased corneal immune cell infiltration, which correlated with nerve loss.

Full summary

419 CHARS

This cross-sectional study investigated corneal confocal microscopy (CCM) in 20 patients with hereditary transthyretin amyloidosis (6 with cardiomyopathy, 14 with polyneuropathy), 5 presymptomatic carriers, and 20 healthy controls. CNFD was also significantly lower in presymptomatic carriers. Findings suggest CCM could be a predictive biomarker for disease onset and indicate immune involvement in amyloid neuropathy.

PICO

PPOPULATION

20 patients with hereditary transthyretin amyloidosis (ATTRv), 5 presymptomatic carriers, and 20 age- and sex-matched healthy controls

IINTERVENTION

Corneal confocal microscopy assessment of corneal nerve fibre density, nerve fibre length, nerve branch density, and cell infiltrates

OOUTCOME

Corneal nerve fibre parameters and immune cell infiltrates

STUDY TYPE

cross-sectional

SPECIALTY

ophthalmology

SUMMARISED BY

AI pipeline

FIDELITY CHECK

100% · A

ORIGINAL PAPER

PMC10267010

Corneal confocal microscopy identifies corneal nerve loss and increased Langerhans cells in presymptomatic carriers and patients with hereditary transthyretin amyloidosis

Journal of Neurology

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ABSTRACT

Abstract Background Hereditary transthyretin amyloidosis (ATTRv amyloidosis) is a rare, but life-threatening protein misfolding disorder due to TTR gene mutations. Cardiomyopathy (ATTRv-CM) and polyneuropathy (ATTRv-PN) with early small nerve fibre involvement are the most common manifestations. Timely diagnosis and treatment initiation are key to limiting progression of disease. Corneal confocal microscopy (CCM) is a non-invasive method to quantify corneal small nerve fibres and immune cell infiltrates in vivo. Methods This cross-sectional study investigated the utility of CCM in 20 patients with ATTRv amyloidosis (ATTRv-CM, n = 6; ATTRv-PN, n = 14) and presymptomatic carriers (n = 5) compared to 20 age- and sex-matched healthy controls. Corneal nerve fibre density, corneal nerve fibre length, corneal nerve branch density, and cell infiltrates were assessed. Results Corneal nerve fibre density and nerve fibre length were significantly lower in patients with ATTRv amyloidosis compared to healthy controls regardless of the clinical phenotype (ATTRv-CM, ATTRv-PN) and corneal nerve fibre density was significantly lower in presymptomatic carriers. Immune cell infiltrates were only evident in patients with ATTRv amyloidosis, which correlated with reduced corneal nerve fibre density. Conclusions CCM identifies small nerve fibre damage in presymptomatic carriers and symptomatic patients with ATTRv amyloidosis and may serve as a predictive surrogate marker to identify individuals at risk of developing symptomatic amyloidosis. Furthermore, increased corneal cell infiltration suggests an immune-mediated mechanism in the pathogenesis of amyloid neuropathy. Supplementary Information The online version contains supplementary material available at 10.1007/s00415-023-11689-z. Keywords: Small fibre neuropathy, PADO concept, siRNA, Hereditary amyloidosis, Immune cells

CITATION EXPORT

Andreas Thimm, Alexander Carpinteiro, Sara Oubari et al.. Corneal confocal microscopy identifies corneal nerve loss and increased Langerhans cells in presymptomatic carriers and patients with hereditary transthyretin amyloidosis. Journal of Neurology. (2023). https://doi.org/10.1007/s00415-023-11689-z

AUTHORS

13 · 8 CENTRES

Andreas Thimm, Alexander Carpinteiro, Sara Oubari, Maria Papathanasiou, Lukas Kessler, Christoph Rischpler, Rayaz Ahmed Malik, Ken Herrmann, Hans Christian Reinhardt, Tienush Rassaf, Christoph Kleinschnitz, Tim Hagenacker, Mark Stettner

1Department of Neurology, University Hospital Essen, Hufelandstrasse 55, 45147 Essen, Germany
2Center for Translational Neuro- and Behavioral Scienes (C-TNBS), University Hospital Essen, Essen, Germany
3Department of Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen, Essen, Germany
4Institute of Molecular Biology, University of Duisburg-Essen, Essen, Germany
5Department of Cardiology and Vascular Medicine, West German Heart and Vascular Center, University Hospital Essen, Essen, Germany
6Department of Nuclear Medicine, University Hospital Essen, Essen, Germany
7Institute of Cardiovascular Science, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK
8Weill Cornell Medicine-Qatar, Education City, Doha, Qatar