Cornea Nerves Can Identify Different Types of Parkinson's Disease

Abstract

Purpose: To investigate whether the cornea nerve can distinguish between different subtypes of Parkinson's disease.

Methods: A total of 63 patients diagnosed with Parkinson's disease-comprising tremor-dominant (TD), postural instability and gait disturbance (PIGD), and mixed subtypes-were included alongside 31 age- and gender-matched control participants. All participants underwent In vivo confocal microscopy (IVCM) examinations along with comprehensive assessments of clinical neurological symptoms using the Movement Disorders Society Unified Parkinson's Disease Rating Scale, Hoehn and Yahr stages, and Montreal Cognitive Assessment scores. The detection range of IVCM includes the indicators of central and inferior whorl-like cornea nerve.

Results: This study involved 63 patients, 23 were classified as having the TD type, 30 as having the PIGD type, and 10 as mixed type. Among them, most of central and whorl-like corneal nerve indicators were significantly lower in the PIGD group compared to the TD group. Receiver operating characteristic analysis demonstrated that combined central and inferior whorl-like corneal nerve indicators exhibited high discriminatory power between TD and PIGD types, with an area under the curve of 0.969.

Conclusions: As a non-invasive examination method, IVCM holds significant value for differentiating Parkinson's disease subtypes and identifying patients with varying motor manifestations. Among these findings, individuals with PIGD displayed more pronounced corneal nerve damage; furthermore, patients exhibiting lower inferior whorl length, corneal nerve fiber width, and fractal dimension of corneal nerves values were found to be at greater risk of being classified within the PIGD subtype.

Figure 1.

IVCM images of cornea central area. Representative IVCM images in (a, e) a healthy control and patient with (b, f) TD, (c, g) PIGD, and (d, h) mixed disease. (a–d) The original images of the IVCM (e–h). The nerve fiber trunk is shown in red, with green dots indicating the origin of the branch and blue representing the branch nerves.

Figure 2.

IVCM images of cornea inferior whorl-like area. Representative IVCM images in (a, e) a healthy control and patient with (b, f) TD, (c, g) PIGD, and (d, h) mixed disease. (a–d) The original images of the IVCM (e–h). The nerve fiber trunk is shown in red, with green dots indicating the origin of the branch and blue representing the branch nerves.

Figure 3.

IVCM measurements in patients with PD of different motor subtypes. Scatter plots of (a) CNFL, (b) CNFrD, (c) IWL and, (d) IWFrD in the Control, TD, PIGD, and mixed groups. *P < 0.05; ***P < 0.001.

Figure 4.

The ROC for IVCM distinguishing PD from Control (a). The ROC for IVCM distinguishing TD from PIGD (b).

Figure 5.

Correlation analysis in three groups. (a–d) The correlation analysis between the MDS-UPDRS III and CNFA, CNFrD, CNBD and CTBD. (e, f) The correlation analysis between the MoCA and CNFrD and CNFA.