Pupillometric findings in ATTRv patients and carriers: results from a single-centre experience

Abstract

Introduction

Hereditary transthyretin amyloidosis (ATTRv) is a treatable multisystemic disease with great phenotypic heterogeneity. Among extra-neurological features, pupillary abnormalities have been reported, either related to amyloid deposition in the eye or to a progressive autonomic neuropathy.

Objective

To evaluate the role of automated pupillometry, a non-invasive and rapid test able to provide objective and reproducible data on pupil size and reactivity, as a marker of disease severity in late-onset ATTRv patients.

Patients and methods

We performed automated pupillometry on a cohort of ATTRv patients and pre-symptomatic TTR mutation carriers and compared results to healthy controls. An exhaustive clinical and instrumental evaluation was performed on all enrolled subjects.

Results

A statistically significant difference in most pupillometry parameters was found in ATTRv patients as compared to both carriers and healthy controls. Moreover, in ATTRv patients, we found a significant correlation between many pupillometry findings and disease duration, as well as widely accepted clinical scales and investigations (NIS, Sudoscan from feet, and Norfolk QoL-DN questionnaire).

Conclusions

We suggest pupillometry may play a role as a reliable and non-invasive biomarker to evaluate ATTRv disease severity and monitor its progression.

Keywords:

• Amyloid
• biomarkers
• dysautonomia
• pupillometry
• progression

Acknowledgments

M.L. and M.S. are members of the European Reference Network for Neuromuscular Diseases (Project ID n° 870177).

Disclosure statement

Dr Romano received financial grants (honoraria and speaking) from Akcea, and travel grants from Akcea, Alnylam, Pfizer and Csl Behring; Dr Di Paolantonio received financial grants (honoraria and speaking) from Akcea, Alnylam, Sobi, and travel grants from Akcea; Dr Bisogni received financial grants (honoraria and speaking) from Alnylam, and travel grants from Pfizer, Kedrion and Grifols; Dr M. Sabatelli received financial grants (honoraria and speaking) from Akcea; Dr Luigetti received SOBI, and travel grants from Akcea, Alnylam, Sobi, Pfizer, Kedrion, Csl Behring, and Grifols. Dr Guglielmino, Dr Della Marca, Dr Minnella, Dr Maceroni, Dr Bellavia, Dr Scala, Dr E. Sabatelli and Dr Rollo reported no disclosures.

Data availability statement

The data that support the findings of this study are available from the corresponding author, upon reasonable request.

Additional information

Funding

The present study was supported by an Investigator-Initiated Research to Fondazione Policlinico Universitario Agostino Gemelli IRCCS from Pfizer Inc. Pfizer Inc. had no role in the study design, data analysis, and results interpretation of the present study.