Corneal nerve loss measured by corneal confocal microscopy predicts pain severity in Parkinson's disease

Pain is one of the most prevalent and upsetting symptoms of Parkinson's disease (PD), possibly linked to small fiber neuropathy (SFN). We evaluated small nerve fiber damage in PD patients through corneal confocal microscopy (CCM) and investigated its relationship to pain.

68 PD patients and 31 healthy controls (HC) underwent CCM. Motor and non-motor symptom scales were used to evaluate the recruited PD patients. The patients were divided into two groups: PD with pain (PD-P) and PD with no pain (PD-NP).

Compared to the HC and PD-NP group, PD-P exhibited significant reductions in corneal nerve fiber density (CNFD, P < 0.001), length (CNFL, P < 0.05), and fractal dimension (CNFrD, P < 0.01). Corneal parameters demonstrated significant negative correlations with pain severity, as well as measures of anxiety (HAMA) (all P < 0.05). Mediation analysis indicated that anxiety partially mediated the relationship between corneal nerve loss and pain. Principal component analysis condensed nerve parameters into one component explaining 81.58 % of variance, which strongly correlated with pain scores. Logistic regression identified low CNFD as an independent risk factor for PD-related pain (P < 0.01). Furthermore, corneal nerve parameters, particularly a combination of CNFD, CNFL, and CNFrD, effectively discriminated PD-P from PD-NP patients, achieving an area under the curve (AUC) of 0.80.

Corneal nerve degeneration is significantly associated with pain in PD and may serve as an independent biomarker. SFN likely contributes to peripheral pain mechanisms in PD, involving complex peripheral and central interactions.