Retinal Changes in Double-Antibody Seronegative Neuromyelitis Optica Spectrum Disorders

Abstract

Background and objectives: To systematically describe the clinical picture of double-antibody seronegative neuromyelitis optica spectrum disorders (DN-NMOSD) with specific emphasis on retinal involvement.

Methods: Cross-sectional data of 25 people with DN-NMOSD (48 eyes) with and without a history of optic neuritis (ON) were included in this study along with data from 25 people with aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorder (AQP4-NMOSD, 46 eyes) and from 25 healthy controls (HCs, 49 eyes) for comparison. All groups were matched for age and sex and included from the collaborative retrospective study of retinal optical coherence tomography (OCT) in neuromyelitis optica (CROCTINO). Participants underwent OCT with central postprocessing and local neurologic examination and antibody testing. Retinal neurodegeneration was quantified as peripapillary retinal nerve fiber layer thickness (pRNFL) and combined ganglion cell and inner plexiform layer thickness (GCIPL).

Results: This DN-NMOSD cohort had a history of [median (inter-quartile range)] 6 (5; 9) attacks within their 5 ± 4 years since onset. Myelitis and ON were the most common attack types. In DN-NMOSD eyes after ON, pRNFL (p < 0.001) and GCIPL (p = 0.023) were thinner compared with eyes of HCs. Even after only one ON episode, DN-NMOSD eyes already had considerable neuroaxonal loss compared with HCs. In DN-NMOSD eyes without a history of ON, pRNFL (p = 0.027) and GCIPL (p = 0.022) were also reduced compared with eyes of HCs. However, there was no difference in pRNFL and GCIPL between DN-NMOSD and AQP4-NMOSD for the whole group and for subsets with a history of ON and without a history of ON-as well as between variances of retinal layer thicknesses.

Discussion: DN-NMOSD is characterized by severe retinal damage after ON and attack-independent retinal neurodegeneration. Most of the damage occurs during the first ON episode, which highlights the need for better diagnostic markers in DN-NMOSD to facilitate an earlier diagnosis as well as for effective and early treatments. In this study, people with DN-NMOSD presented with homogeneous clinical and imaging findings potentially suggesting a common retinal pathology in these patients.

Figure 1. Retinal Layer Thicknesses in DN-NMOSD, AQP4-NMOSD, and HCs

Box plots with dotted overlay for single-eye–based values for eyes with a history of ON (orange) and without a history of ON (blue) as well as for HC eyes (gray). Dots are shaped depending on the history of contralateral ON (history of contralateral ON: square, no history of contralateral ON: triangle, HC: circle). AQP4-NMOSD = people with aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorder; DN-NMOSD = people with double-antibody seronegative neuromyelitis optica spectrum disorder; GCIPL = combined ganglion cell and inner plexiform layer; HC = healthy control; INL = inner nuclear layer; MV = macular volume; n.s. = not significant; ON = optic neuritis; pRNFL = peripapillary retinal nerve fiber layer.

Figure 2. Retinal Neurodegeneration After ON in DN-NMOSD and AQP4-NMOSD

Mean layer thickness (dot) with standard error of the mean (whiskers) for eyes without ON (NON, blue) as well as for eyes after 1 ON, 2 ON, and ≥3 ON (orange) of people with DN-NMOSD (left) and AQP4-NMOSD (right). Owing to the low sample size, none of the within-group comparisons (NON vs 1 ON, 1 ON vs 2 ON, 2 ON vs ≥3 ON) was statistically significant. AQP4-NMOSD = people with aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorder; DN-NMOSD = people with double-antibody seronegative neuromyelitis optica spectrum disorder; GCIPL = combined ganglion cell and inner plexiform layer; ON = optic neuritis; pRNFL = peripapillary retinal nerve fiber layer.