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. 2021 Oct;27(11):1738-1748.
doi: 10.1177/1352458520977771. Epub 2020 Dec 14.

Evidence of subclinical quantitative retinal layer abnormalities in AQP4-IgG seropositive NMOSD

Angeliki G Filippatou  1 , Eleni S Vasileiou  1 , Yufan He  2 , Kathryn C Fitzgerald  1 , Grigorios Kalaitzidis  1 , Jeffrey Lambe  1 , Maureen A Mealy  3 , Michael Levy  4 , Yihao Liu  2 , Jerry L Prince  2 , Ellen M Mowry  1 , Shiv Saidha  1 , Peter A Calabresi  1 , Elias S Sotirchos  1
Affiliations

Evidence of subclinical quantitative retinal layer abnormalities in AQP4-IgG seropositive NMOSD

Angeliki G Filippatou et al. Mult Scler. 2021 Oct.

Abstract

Background: Prior studies have suggested that subclinical retinal abnormalities may be present in aquaporin-4 immunoglobulin G (AQP4-IgG) seropositive neuromyelitis optica spectrum disorder (NMOSD), in the absence of a clinical history of optic neuritis (ON).

Objective: Our aim was to compare retinal layer thicknesses at the fovea and surrounding macula between AQP4-IgG+ NMOSD eyes without a history of ON (AQP4-nonON) and healthy controls (HC).

Methods: In this single-center cross-sectional study, 83 AQP4-nonON and 154 HC eyes were studied with spectral-domain optical coherence tomography (OCT).

Results: Total foveal thickness did not differ between AQP4-nonON and HC eyes. AQP4-nonON eyes exhibited lower outer nuclear layer (ONL) and inner photoreceptor segment (IS) thickness at the fovea (ONL: -4.01 ± 2.03 μm, p = 0.049; IS: -0.32 ± 0.14 μm, p = 0.029) and surrounding macula (ONL: -1.98 ± 0.95 μm, p = 0.037; IS: -0.16 ± 0.07 μm, p = 0.023), compared to HC. Macular retinal nerve fiber layer (RNFL: -1.34 ± 0.51 μm, p = 0.009) and ganglion cell + inner plexiform layer (GCIPL: -2.44 ± 0.93 μm, p = 0.009) thicknesses were also lower in AQP4-nonON compared to HC eyes. Results were similar in sensitivity analyses restricted to AQP4-IgG+ patients who had never experienced ON in either eye.

Conclusions: AQP4-nonON eyes exhibit evidence of subclinical retinal ganglion cell neuronal and axonal loss, as well as structural evidence of photoreceptor layer involvement. These findings support that subclinical anterior visual pathway involvement may occur in AQP4-IgG+ NMOSD.

Keywords: Neuromyelitis optica; aquaporin-4; fovea; optical coherence tomography; retina.

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Conflict of interest statement

Conflict of Interest

The authors report no conflict of interest.

Figures

Figure 1
Figure 1
Boxplots of macular retinal layer thicknesses (excluding the fovea) in HC and AQP4 non-ON eyes: (a.) TRT (b.) RNFL (c.) GCIPL (d.) ONL (e.) IS (f.) ONLPS HC: healthy controls; AQP4: aquaporin-4; ON: optic neuritis; TRT: total retinal thickness; RNFL: retinal nerve fiber layer; GCIPL: ganglion cell+inner plexiform layer; ONL: outer nuclear layer; IS: inner photoreceptor segment; ONLPS: outer nuclear layer & photoreceptor segments
Figure 2
Figure 2
Boxplot of foveal thickness in HC and AQP4 non-ON eyes HC: healthy controls; AQP4: aquaporin-4; ON: optic neuritis
Figure 3
Figure 3
Boxplots of foveal retinal layer thicknesses in HC and AQP4 non-ON eyes: (a.) ONL (b.) IS (c.) ONLPS HC: healthy controls; AQP4: aquaporin-4; ON: optic neuritis; ONL: outer nuclear layer; IS: inner photoreceptor segment; ONLPS: outer nuclear layer & photoreceptor segments
Figure 4
Figure 4
Boxplot of pRNFL in HC and AQP4 non-ON eyes HC: healthy controls; AQP4: aquaporin-4; ON: optic neuritis; pRNFL: peripapillary retinal nerve fiber layer
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