To describe corneal nerve fiber length (CNFL) in hereditary transthyretin amyloidosis (hATTR) polyneuropathy.

Transthyretin hereditary amyloidosis (hATTR) is a progressive, multi-system disease, that includes degeneration of small and large nerve fibers.  In vivo Corneal Confocal Microscopy (IVCCM) has emerged as an important tool for the evaluation of small nerve fiber structure and has been associated with both large and small-fiber neuropathy in diabetes mellitus. It shows comparable performance for small nerve fibers to Intraepidermal Nerve Fiber Density evaluation, with the advantage of being non-invasive.  CNFL is the most sensitive IVCCM parameter to detect small-fiber neuropathy and can be abnormal before large-fiber neuropathy is demonstrable.

We performed a retrospective cross-sectional study of hATTR patients who had IVCCM and automated CNFL measurements, clinical assessments and nerve conduction studies (NCS) from February to October 2019. CNFL ≤10.7 mm/mm2 is the normal cut-off according to our laboratory normative values.

We included 9 patients, 1/3 female, with a mean age 61.7±8.8 years,  and age of neuropathy onset 56.9±9.0 years. Of these, 8 (88%) had abnormal NCS and all had abnormal CNFL. Mean CNFL was 7.49 ± 1.70 mm/^mm2 (range 4.71- 9.90 mm/mm²). Sural nerve sensory potentials were abnormal in 7 patients. There was a trend to a negative association between age (r=-0.56) and age of neuropathy onset (r=-0.59) with CNFL.

In patients with hATTR polyneuropathy, CNFL is able to detect impairment in small nerve fibers and may prove useful in detection of early neuropathy and early response to therapy.  Further studies are needed to assess CNFL in various stages of hATTR neuropathy and the reliability of this measure in monitoring disease progression.