Astrocytic outer retinal layer thinning is not a feature in AQP4-IgG seropositive neuromyelitis optica spectrum disorders
Authors: Lu Angelo , Zimmermann Hanna G , Specovius Svenja , Motamedi Seyedamirhosein , Chien Claudia , Bereuter Charlotte , Lana-Peixoto Marco A , Fontenelle Mariana Andrade , Ashtari Fereshteh , Kafieh Rahele , Dehghani Alireza , Pourazizi Mohsen , Pandit Lekha , D'Cunha Anitha , Kim Ho Jin , Hyun Jae-Won , Jung Su-Kyung , Leocani Letizia , Pisa Marco , Radaelli Marta , Siritho Sasitorn , May Eugene F , Tongco Caryl , De Sèze Jérôme , Senger Thomas , Palace Jacqueline , Roca-Fernández Adriana , Leite Maria Isabel , Sharma Srilakshmi M , Stiebel-Kalish Hadas , Asgari Nasrin , Soelberg Kerstin Kathrine , Martinez-Lapiscina Elena H , Havla Joachim , Mao-Draayer Yang , Rimler Zoe , Reid Allyson , Marignier Romain , Cobo-Calvo Alvaro , Altintas Ayse , Tanriverdi Uygur , Yildirim Rengin , Aktas Orhan , Ringelstein Marius , Albrecht Philipp , Tavares Ivan Maynart , Bichuetti Denis Bernardi , Jacob Anu , Huda Saif , Soto de Castillo Ibis , Petzold Axel , Green Ari J , Yeaman Michael R , Smith Terry J , Cook Lawrence , Paul Friedemann , Brandt Alexander U , Oertel Frederike Cosima 
Published: October 2021

Background

Patients with anti-aquaporin-4 antibody seropositive (AQP4-IgG+) neuromyelitis optica spectrum disorders (NMOSDs) frequently suffer from optic neuritis (ON) leading to severe retinal neuroaxonal damage. Further, the relationship of this retinal damage to a primary astrocytopathy in NMOSD is uncertain. Primary astrocytopathy has been suggested to cause ON-independent retinal damage and contribute to changes particularly in the outer plexiform layer (OPL) and outer nuclear layer (ONL), as reported in some earlier studies. However, these were limited in their sample size and contradictory as to the localisation. This study assesses outer retinal layer changes using optical coherence tomography (OCT) in a multicentre cross-sectional cohort.

Method

197 patients who were AQP4-IgG+ and 32 myelin-oligodendrocyte-glycoprotein antibody seropositive (MOG-IgG+) patients were enrolled in this study along with 75 healthy controls. Participants underwent neurological examination and OCT with central postprocessing conducted at a single site.

Results

No significant thinning of OPL (25.02±2.03 µm) or ONL (61.63±7.04 µm) were observed in patients who were AQP4-IgG+ compared with patients who were MOG-IgG+ with comparable neuroaxonal damage (OPL: 25.10±2.00 µm; ONL: 64.71±7.87 µm) or healthy controls (OPL: 24.58±1.64 µm; ONL: 63.59±5.78 µm). Eyes of patients who were AQP4-IgG+ (19.84±5.09 µm, p=0.027) and MOG-IgG+ (19.82±4.78 µm, p=0.004) with a history of ON showed parafoveal OPL thinning compared with healthy controls (20.99±5.14 µm); this was not observed elsewhere.

Conclusion

The results suggest that outer retinal layer loss is not a consistent component of retinal astrocytic damage in AQP4-IgG+ NMOSD. Longitudinal studies are necessary to determine if OPL and ONL are damaged in late disease due to retrograde trans-synaptic axonal degeneration and whether outer retinal dysfunction occurs despite any measurable structural correlates.