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

Abstract

Objective: To investigate disease-specific foveal shape changes in patients with neuromyelitis optica spectrum disorders (NMOSDs) using foveal morphometry.

Methods: This 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.

Results: Group 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.

Conclusions: Foveal 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.

Figure 1. Three-dimensional foveal shape analysis method overview

(A) ILM surface smoothing and radial reconstruction using the cubic Bezier polynomial. (B) Rim height, average pit depth, and central foveal thickness. (C) Rim disk (blue), slope disk (red), and pit flat disk (green) and major and minor axes on each surface. (D) Rim volume, pit volume, and inner rim volume. APD = average pit depth, CFT = central foveal thickness; ILM = inner limiting membrane; major = major axis; minor = minor axis.

Figure 2. ROC curves, exploratory data analysis for selected parameters, and sample fovea

ROC curves for best-performing foveal shape and standard OCT parameters discriminating between (A) NMOSD vs MS, (B) NMOSD ON− vs MS ON−, and (C) NMOSD ON + vs MS ON+. Box and dot plots for (D) pit flat disk area, (E) average pit flat disk diameter, (F) inner rim volume, and (G) major slope disk length, the selected 4 foveal shape parameters. (H) Rim volume and (I) average pit depth, as example foveal shape parameters affected by ON but not diagnosis. A sample central (foveal) B scan of (J) MS ON− and (K) NMOSD ON−, chosen from the median of the selected pit flat disk parameters in each group, demonstrating the difference in foveal pit (pit flat disk), between NMOSD and MS in eyes without a history of ON. AUC = area under the curve; FT = foveal thickness; pRNFL = peripapillary retinal nerve fiber layer thickness; INL = inner nuclear layer volume; HC = healthy controls; MS = patients with MS; NMOSD = patients with neuromyelitis optica spectrum disorders; ON = optic neuritis; ON− = eyes without a history of ON; ON+ = eyes with a history of ON; ROC = receiver operating characteristic.