O-PN003. Corneal sub-basal whorl-like nerve plexus: A landmark for early and follow-up evaluation in transthyretin familial amyloid polyneuropathy

Abstract

Introduction . To evaluate the quantification of corneal sub-basal whorl-like nerve plexus parameters as a sensitive and static marker in early diagnosis of small fiber neuropathy (SFN) and monitor disease progression in familial amyloid polyneuropathy (FAP) patients. Methods . Fifteen FAP patients and fifteen healthy controls underwent neurological evaluation (including clinical scales and electrophysiological tests) and corneal nerve observation. Corneal nerve fiber density (CNFD), Corneal nerve fiber branch density (CNBD), Corneal nerve fiber length (CNFL) were detected in the central cornea (conventional method) and the whorl-like inferocentral cornea (new method). The Langerhans cells (LC) density in each image was calculated. Results . Corneal parameters were significantly reduced with disease progression. Only inferior whorl length (IWL) was significantly reduced in preclinical patients (with normal SSR and CHEPs results) comparing with age matched controls. IWL, CNFL, CNBD and CNFD were significantly lower in early phase patients. LC density was significantly increased around the central whorl in early phase patients than in healthy controls (p = 0.009), and was lower in the progressive patients. Both IWL and CNFL correlated with severity of neuropathy. IWL was more significantly reduced with the progression of disease than CNFL. The area under the ROC curve to distinguish FAP with CNFL and IWL was 88.0% and 89.3%, respectively, exceeding other parameters. The coefficient of variation of the IWL value was significantly (P < 0.0001) smaller than that of the conventional method. Conclusion . The observation of corneal sub-basal whorl-like nerve plexus can detect SFN in preclinical FAP patients earlier than traditional electrophysiological methods. IWL is the most sensitive and reliable parameters and it can best discriminate FAP patients from controls. The clustering of immature LCs at the whorl area might reflect the inflammatory response of small- fiber nerves at the very early stage.