CNS Involvement in Chronic Inflammatory Demyelinating Polyneuropathy: Subtle Retinal Changes in Optical Coherence Tomography

Abstract

Background and objectives: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune disease primarily affecting the peripheral nervous system. However, several noncontrolled studies have suggested concomitant inflammatory CNS demyelination similar to multiple sclerosis. The aim of this study was to investigate an involvement of the visual pathway in patients with CIDP.

Methods: In this prospective cross-sectional study, we used high-resolution spectral-domain optical coherence tomography to compare the thickness of the peripapillary retinal nerve fiber layer and the deeper macular retinal layers as well as the total macular volume (TMV) in 22 patients with CIDP and 22 age-matched and sex-matched healthy control (HC) individuals. Retinal layers were semiautomatically segmented by the provided software and were correlated with clinical measures and nerve conduction studies.

Results: In patients with CIDP compared with healthy age-matched and sex-matched controls, we found slight but significant volume reductions of the ganglion cell/inner plexiform layer complex (CIDP 1.86 vs HC 1.95 mm³, p = 0.015), the retinal pigment epithelium (CIDP 0.38 vs HC 0.40 mm³, p = 0.02), and the TMV (CIDP 8.48 vs HC 8.75 mm³, p = 0.018). The ganglion cell layer volume and motor nerve conduction velocity were positively associated (B = 0.002, p = 0.02).

Discussion: Our data reveal subtle retinal neurodegeneration in patients with CIDP, providing evidence for visual pathway involvement, detectable by OCT. The results need corroboration in independent, larger cohorts.

Figure 1. Flowchart of Subject Recruitment

Patients with CIDP and healthy controls were recruited at the Department of Neurology, Heinrich-Heine-University in Düsseldorf, Germany. Of the 66 individuals, 44 were patients with CIDP and 22 healthy control subjects. Of the 44 patients with CIDP who were screened, 22 individuals were excluded because of concomitant diabetes mellitus and ophthalmic pathologies. Additional 7 single eyes were excluded because of drusen and macular edema. Of the remaining individuals, 22 were patients with CIDP and 22 age- and sex-matched controls. CIDP = chronic inflammatory demyelinating polyneuropathy.

Figure 2. OCT Measurements

(A) The macular thickness and volume were calculated from consecutive vertical scans centered on the macula. (B) The peripapillary RNFL was evaluated in a circular scan centered on the optic disk. (C) The deeper retinal layers were semiautomatically segmented in a single horizontal foveal scan. The volumes of the retinal layers were assessed by averaging 14 images from vertical scans. (D) Scatter plots display the macular layer volumes or thickness. All values are described as mean ± SD. Each point represents 1 eye. The mean of all eyes is represented by the horizontal line. Statistical differences in patients with CIDP vs healthy controls were assessed by GEE accounting for several measurements in the same individual (2 eyes). GEE = generalized estimation equation; mGCIPL = macular ganglion cell/inner plexiform layer; mGCL = macular ganglion cell layer; mINL = macular inner nuclear layer; mIPL = macular inner plexiform layer; mONL = macular outer nuclear layer; mOPL = macular outer plexiform layer; mRNFL = macular retinal nerve fiber layer; OCT = optical coherence tomography; pRNFL = peripapillary retinal nerve fiber layer; RPE = retinal pigment epithelium; TMV = total macular volume.

Figure 3. Analysis of Associations With Neurographic and Clinical Features

Scatter plots of associations of retinal layers with nerve conduction and compound action potential amplitudes of the right ulnar nerve, as well as time since disease manifestation in patients with CIDP vs. healthy controls. Each dot represents 1 eye, p values (GEE method), and regression lines are provided. (A) Positive association of MNCV with mGCL (p = 0.021). (B) Negative association of CMAP with mRPE (p = 0.009). (C) Negative association of SNCV with TMV (p = 0.009). (D and E) Positive association of the time of OCT measurement since disease manifestation with TMV (D, p = 0.005) and mIPL (E, p = 0.015). CIDP = chronic inflammatory demyelinating polyneuropathy; CMAP = compound motor action potential; GEE = generalized estimation equation; mGCL, macular ganglion cell layer; mIPL, macular inner plexiform layer; MNCV, motor nerve conduction velocity; mRPE, macular retinal pigment epithelium; SNCV, sensory nerve conduction velocity; TMV, total macular volume.