Corneal Confocal Microscopy Identifies Corneal Nerve Loss and Increased Langerhans Cells in Presymptomatic Carriers and Patients with Hereditary Transthyretin Amyloidosis

Overview

Journal J Neurol

Specialty Neurology

Date 2023 Apr 4

PMID 37014422

Authors

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

Affiliations

Soon will be listed here.

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.

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