Corneal Confocal Microscopy Shows Potential for Monitoring CIDP, Limited Diagnostic Use

Rafael Klimas, MD

(Credit: LinkedIn)

In a recent study, investigators assessed corneal confocal microscopy (CCM) in diagnosing and monitoring chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), an autoimmune neuropathy characterized by recurring or progressively worsening weakness and sensory impairments. Published in the Journal of Neurology, results showed that although CCM correlated with disease severity, its diagnostic accuracy fell short for routine clinical application.¹

The study analyzed 100 patients with CIDP and 31 healthy controls to assess CCM parameters, including corneal nerve fiber density, length, and branch density. Patients with CIDP displayed significant reductions in these measures, particularly in advanced disease stages and those with higher disability scores. CCM findings were also associated with sensory axonal pathology identified via electroneurography, but its sensitivity (41%) and specificity (77%) limited its standalone diagnostic value.

“In this study, we demonstrate the ability of CCM to detect degenerative axonal damage. Firstly, our data show that CCM can differentiate between healthy controls and CIDP-patients. Furthermore, it is even possible to distinguish between CIDP subgroups and healthy subjects. Interestingly, no significant differences between [multifocal acquired demyelinating sensory and motor neuropathy] and healthy controls were observed, which might be due to the small sample size,” lead author Rafael Klimas, MD, an assistant doctor in neurology at St. Josef-Hospital Clinic of Ruhr-University in Bochum, Germany, and colleagues noted.¹

Between January 2018 and October 2023, patients with CIDP recruited from the Immune-mediated Neuropathies Biobank (INHIBIT) registry were analyzed for the study. All patients underwent standardized clinical and paraclinical evaluations and were diagnosed based on the European Federation of Neurological Societies/Peripheral Nerve Society diagnostic criteria.² A group of healthy controls, without polyneuropathy, diabetes, or alcohol abuse, was included for comparison. Data collected encompassed sociodemographic information, CIDP subtypes, clinical scores, nerve conduction studies, and CCM measurements.

READ MORE: Long-Term Disability of Chronic Demyelinating Polyradiculoneuropathy Lessened With Early Treatment Initiation

All told, patients with higher overall disability sum score scores exhibited significantly reduced axonal CCM parameters compared with healthy controls. Likewise, lower CCM parameter values were linked to higher sensory sum score scores, indicating greater sensory impairment. In contrast, the inflammatory Rasch-built overall disability scale, which assesses daily functional activities, did not follow this pattern. Although there were some associations between CCM parameters and these clinical scores, no significant correlations were identified, suggesting a nonlinear relationship between clinical measures and axonal damage as assessed by CCM.

Authors noted that this study had certain limitations. Although using quartiles to define disease stages was considered a helpful approach, it reduced the sample size available for analysis. Conducting a longitudinal follow-up of patients with CIDP from the point of initial diagnosis could potentially provide a more comprehensive assessment of CCM’s role, particularly in evaluating axonal degeneration.

“One potential reason for the low sensitivity and specificity might be due to the reduction of CCM parameters predominantly in the later stages of the disease. Since these disease stages are less characterized by neuroinflammation but rather by neurodegeneration, CCM might primarily correlate with signs of axonal degeneration which weakens its value as a diagnostic tool,” Klimas et al noted.¹ “Especially early disease stages are predominantly characterized by peripheral neuroinflammation. However, no correlation of CCM parameters and clinical scores was found for early stages of this disease. These results might emphasize the role of CCM for monitoring disease progression and axonal pathology.”

REFERENCES
1. Klimas R, Sturm D, Altenborg A, et al. Assessing axonal pathology and disease progression in chronic inflammatory demyelinating polyneuropathy using corneal confocal microscopy. J Neurol. 2024;272(1):51. Published 2024 Dec 12. doi:10.1007/s00415-024-12812-4
2. Joint Task Force of the EFNS and the PNS. European Federation of Neurological Societies/Peripheral Nerve Society Guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society. J Peripher Nerv Syst. 2005;10(3):220-228. doi:10.1111/j.1085-9489.2005.10302.x