Corneal sub‐basal whorl‐like nerve plexus: a landmark for early and follow‐up evaluation in transthyretin familial amyloid polyneuropathy

Abstract

Background and purposeSmall‐fiber nerves are the first to be involved in transthyretin familial amyloid polyneuropathy (TTR‐FAP) patients. In vivo corneal confocal microscopy (CCM) is a noninvasive technique to detect small‐fiber polyneuropathy (SFN) by quantifying corneal nerve morphology. The characteristic whorl‐like pattern of the corneal nerve provides a static landmark for observation. We aimed to evaluate whether CCM images of the whorl‐like plexus can sensitively evaluate and monitor disease progression in FAP patients.MethodsFifteen FAP patients and 15 controls underwent neurological evaluation and CCM observation. Corneal nerve fiber length (CNFL), corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD) detected by conventional method and inferior whorl length (IWL), inferior whorl fiber density (IWFD), and inferior whorl branch density (IWBD) were compared in controls and patients. The Langerhans cell (LC) density in each image was calculated.ResultsAll CCM parameters were significantly reduced with disease progression. Preclinical patients had significantly lower IWL (P = 0.008) than age‐matched controls. IWL (P = 0.006), CNFL (P = 0.005), CNBD (P = 0.008), and CNFD (P = 0.014) were significantly lower in early‐phase patients. LC density was significantly increased around the central whorl in early‐phase patients and was relatively lower in progressive patients. Both IWL and CNFL correlated with the severity of neuropathy, and IWL was more significantly reduced. The area under the receiver operating characteristic (ROC) curve for FAP with CNFL and IWL was 88.0% (95% CI, 70.9%–96.9%) and 89.3% (95% CI, 72.6%–97.6%), respectively, exceeding other parameters.ConclusionsIWL is a more sensitive surrogate to detect preclinical SFN in FAP and can best discriminate patients from controls. The clustering of immature LCs at the inferior whorl area might reflect the inflammatory response of small‐fiber nerves at the early stage.

Distal Corneal Small Nerve Fibre Damage in Subjects With Obesity

“…Comparison of corneal nerve length at the more distal inferior whorl with more proximal central corneal nerves enables an assessment for a dying-back neuropathy. Zhang et al showed that a reduction in inferior whorl length occurred in in patients with sub-clinical familial amyloid polyneuropathy [8]. In a cross-sectional study, we have previously reported greater corneal nerve loss at the IW compared to the central cornea in patients with diabetic neuropathy [9], and there was greater corneal nerve loss at the IW compared to the central cornea in a longitudinal study [10].…”

Corneal Confocal Microscopy to Image Small Nerve Fiber Degeneration: Ophthalmology Meets Neurology

“…This lack of a floor effect increases the utility of CNFL compared to IENFD in longitudinal and interventional studies of amyloid neuropathy. Recently, a study from China has confirmed and extended these findings by showing corneal nerve loss in the central and inferior whorl regions with an AUC for CNFL and IWL of 88.0 and 89.3%, respectively, for the diagnosis of familial amyloid neuropathy ( 57 ).…”

Corneal Confocal Microscopy and the Nervous System: Introduction to the Special Issue

“…The fatal inherited disorder, transthyretin familial amyloid polyneuropathy, is characterized by a progressive neuropathy and cardiomyopathy [ 57 ]; CNFL is reduced in patients with this condition [ 58 ] and has good diagnostic utility [ 59 ].…”