INCAT score for upper and lower extremities was analyzed separately (top row for upper and bottom row for lower extremities). of disease. The number of dendritic cells in proximity to CNFs was increased in patients with early disease and correlated with the degree of motor affection. A further reduction in CNF parameters and an increase in nondendritic cells were observed in patients with painful neuropathy. In CIDP patients with antineuronal antibodies the number of nondendritic cells was increased. == Interpretation == Our findings suggest that CNF loss may reflect severity of neuropathy and quantification of distinct cells around the CNF plexus may help in stratifying CIDP subtypes, clinical course, and disease activity. However , further longitudinal studies are required before CCM can be considered as a valid surrogate endpoint for patients with CIDP and MMN. == Introduction == Immunemediated disorders of the peripheral nervous system (PNS) exhibit a wide variety of clinical presentations and can be challenging in their diagnosis and treatment. 1, 2Despite established criteria to diagnose chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), there is significant clinical heterogeneity in relation to clinical course and response to treatment. 3In atypical cases, CIDP can be difficult to diagnose and a significant number of patients with CIDP remain unrecognized. 4 In addition , the lack of objective and feasible measures to differentiate such subtypes makes it impossible to predict the responsiveness of available therapies. 5Thus, there is an unmet need for subclassifying chronic inflammatory disorders of the PNS with noninvasive techniques to better define the underlying pathology and improve systematic categorization. Corneal confocal microscopy (CCM), a rapid noninvasive ophthalmic imaging technique, has been demonstrated to quantify axonal loss in a variety of peripheral neuropathies including hereditary sensory and autonomic neuropathy, 6CharcotMarieTooth disease type 1A, 7Fabry disease, 8and idiopathic small fiber neuropathy. 9It has also Synaptamide been widely used to evaluate diabetic neuropathy in multiple studies10demonstrating that this technique is a viable surrogate endpoint for early diagnosis, 11stratification of neuropathy severity, 12and assessing the response to treatment. 13This technique is highly reproducible14, 15and welltolerated. 16An automated and standardized image analysis method for quantification of corneal nerve morphology has also been developed. 17, 18 An emerging body of evidence indicates that small fiber involvement Synaptamide and early axonal involvement is present in CIDP. 19, 20As such, CCM may be a useful measure of nerve damage in patients with CIDP. However , studies exploring corneal involvement in CIDP are limited and conflicting to date. While corneal sensitivity was normal, 21a recent study using CCM in 16 patients with CIDP demonstrated corneal nerve fiber (CNF) loss. 22CCM can also quantify the presence and density of Langerhans cells in Bowman’s layer of the cornea in patients with diabetes. 23Using the latest third generation HRT III (Heidelberg retinal tomograph III), it can also be used to classify and quantify Langerhans cells into a adult phenotype (dendritic cells) or an immature phenotype (nondendritic cell) and provide insight into immune alterations in vivo. 24It has been suggested that direct contact between dendritic cells and the subbasal nerve plexus, seen in CCM, may trigger nerve fiber damage. 25 In this study we investigated the potential of CCM as a meaningful diagnostic tool in a large cohort of wellcharacterized patients with CIDP and multifocal motor neuropathy (MMN) compared to control subjects. Detailed quantification of corneal nerve and immune cell morphology was related to electrophysiological parameters, severity of neuropathy, clinical course, response to F2rl1 Synaptamide therapy, and laboratory findings. == Material and Methods == == Patient assessment and diagnostic classification == The study was approved by the local Ethics Committee (Ethics Committee University of Dusseldorf, #4870). All patients gave their written informed consent prior to the inclusion into the study. The study was in accordance with the Declaration of Helsinki. A total of 182 patients and healthy controls were studied of which 88 patients were diagnosed as having CIDP, including 12 neuropathy patients with monoclonal gammopathy of undetermined significance (MGUSN), whereas six patients were classified as suffering from MMN. Patients were recruited between 2014 and 2015 at the Department of Neurology, Dusseldorf, Germany. The diagnoses of CIDP or MMN were based on the respective criteria of the Peripheral Nerve Society/European Federation of Neurological Societies. 26, 27, 28Patients were diagnosed with MGUSN.
