Altered fovea in AQP4-IgG–seropositive neuromyelitis optica spectrum disorders

Abstract

ObjectiveTo investigate disease-specific foveal shape changes in patients with neuromyelitis optica spectrum disorders (NMOSDs) using foveal morphometry.MethodsThis cross-sectional study included macular spectral domain optical coherence tomography scans of 52 eyes from 28 patients with aquaporin-4 immunoglobulin G (AQP4-IgG)-seropositive NMOSD, 116 eyes from 60 patients with MS, and 123 eyes from 62 healthy controls (HCs), retrospectively, and an independent confirmatory cohort comprised 33/33 patients with NMOSD/MS. The fovea was characterized using 3D foveal morphometry. We included peripapillary retinal nerve fiber layer (pRNFL) thickness and combined macular ganglion cell and inner plexiform layer (GCIPL) volume to account for optic neuritis (ON)-related neuroaxonal damage.ResultsGroup comparison showed significant differences compared with HC in the majority of foveal shape parameters in NMOSD, but not MS. Pit flat disk area, average pit flat disk diameter, inner rim volume, and major slope disk length, as selected parameters, showed differences between NMOSD and MS (p value = 0.017, 0.002, 0.005, and 0.033, respectively). This effect was independent of ON. Area under the curve was between 0.7 and 0.8 (receiver operating characteristic curve) for discriminating between NMOSD and MS. Pit flat disk area and average pit flat disk diameter changes independent of ON were confirmed in an independent cohort.ConclusionsFoveal morphometry reveals a wider and flatter fovea in NMOSD in comparison to MS and HC. Comparison to MS and accounting for ON suggest this effect to be at least in part independent of ON. This supports a primary retinopathy in AQP4-IgG–seropositive NMOSD.

Efficacy of Low-Dose Rituximab on Neuromyelitis Optica-Associated Optic Neuritis

“…Although OCT has been used for the evaluation of ON in NMO or MS in many studies, longitudinal observation studies have been rare. It is reported that NMO-ON eyes have lower peri-papillary retinal nerve fiber layer and macular ganglion cell + inner plexiform layer thicknesses, as well as a “flater” disc when compared with MS-ON eyes ( 21 , 37 ). Moreover, while MS-ON mostly affected the small-diameter neurons in the temporal quadrant of the optic disc, NMO-ON more affected the nerve fibers above and below the optic disc ( 38 , 39 ), consistent with the results in this study.…”

Cognitive impairment in NMOSD—More questions than answers

“…In the central nervous system (CNS), the water channel AQP4, involved in the processes of osmoregulation, is highly expressed on astrocytic end‐feet (forming part of the blood–brain barrier) and ventricular ependyma (Mader, Brimberg, & Diamond, 2017; Rosales & Kister, 2016; Wingerchuk, Lennon, Pittock, Lucchinetti, & Weinshenker, 2006). ⁠ Importantly, also Müller cells of the retina express this membrane protein, what can lead to alter fovea shape in AQP4‐IgG(+) patients (Motamedi et al., 2020; Yamamura & Nakashima, 2017). Moreover, AQP4 is widespread in many organs outside CNS, such as kidneys, placenta, stomach, skeletal muscle, lungs, the inner ear, lacrimal and salivary glands, and olfactory epithelial cells (Rosales & Kister, 2016).…”

“…and ventricular ependyma (Mader, Brimberg, & Diamond, 2017;Rosales & Kister, 2016;. Importantly, also Müller cells of the retina express this membrane protein, what can lead to alter fovea shape in AQP4-IgG(+) patients (Motamedi et al, 2020;Yamamura & Nakashima, 2017). Moreover, AQP4 is widespread in many organs outside CNS, such as kidneys, placenta, stomach, skeletal muscle, lungs, the inner ear, lacrimal and salivary glands, and olfactory epithelial cells (Rosales & Kister, 2016).…”

“…Additionally, depression and anxiety, as well as fatigue, are frequently associated with NMOSD and have a significant impact on health-related quality of life (HRQoL) (Whittam et al, 2017). The symptoms associated with other organs, which may occur in NMOSD, encompass primary retinopathy (Motamedi et al, 2020;Yamamura & Nakashima, 2017), asymptomatic hyper-CKemia and corticosteroid-responsive myalgia, microcystic macular edema (MME), hearing loss, and hyposmia (Rosales & Kister, 2016).…”

Spinal cord and brain MRI should be routinely performed during follow-up in patients with NMOSD – Commentary

“…However, there is accumulating evidence for subclinical tissue damage in NMOSD and MOGAD from recent MRI and retinal imaging studies with optical coherence tomography (OCT) even in the absence of clinical symptoms. 8–10 Microstructural brain tissue alterations, spinal cord atrophy, and loss of retinal ganglion cells without brain or spinal cord symptoms or optic neuritis attacks have been repeatedly reported which challenges the current view that tissue damage does not occur independently of relapses in these conditions. However, these findings are still too preliminary to justify routine imaging follow-up in these patients as we cannot judge whether switch of immunotherapy based solely on imaging studies would result in a better prognosis with less long-term disability.…”