ECTRIMS eLearning

Abstract: 212

Type: Scientific Session

Abstract Category: Pathology and pathogenesis of MS - OCT

Introduction: Neuromyelitis Optica Spectrum Disorders (NMOSD) are inflammatory conditions of the central nervous system (CNS) with a monophasic or relapsing course. It remains unclear, if progressive disease and neurodegeneration contribute to disability accrual. Recently, microstructural changes independent of clinical NMOSD attacks have been identified cross-sectionally in the retina and other CNS regions.
Objectives: To longitudinally assess ganglion cell and inner plexiform layer (GCIP) thickness as a marker of neuro-axonal damage in a homogeneous cohort of aquaporin4-antibody (AQP4-IgG) seropositive NMOSD patients without optic neuritis (ON) during follow-up (F/U).
Aims: To investigate longitudinal attack-independent microstructural changes in AQP4-IgG seropositive NMOSD.
Methods: Out of 157 screened NMOSD patients, 94 eyes of 51 AQP4-IgG seropositive patients without ON in F/U (median F/U 2.3 years, age 47.3 ± 14.4 years, female / male 84.3 % / 15.7 %) and 56 eyes of 28 age and sex matched healthy controls (HC; median F/U 2.3 years, age 43.1 ± 9.8 years, female / male 78.6 % / 21.4 %) were included. The NMOSD cohort included 60 eyes without a history of ON (Eye^ON-) and 34 eyes with a history of ON at least five months before baseline (Eye^ON+). Combined ganglion cell and inner plexiform layer (GCIP), peripapillary retinal nerve fibre layer (pRNFL), fovea thickness (FT), inner nuclear layer (INL) and total macular volume (TMV) were measured by optical coherence tomography (OCT). Visual function was assessed by high-contrast visual acuity (VA) in patients.
Results: At baseline, GCIP, FT and TMV were reduced in Eye^ON+ (GCIP p < 2e^-16; FT p = 3.7e^-4; TMV p = 3.7e^-12) but also in Eye^ON- (GCIP p = 0.002; FT p = 0.040; TMV p = 6.1e^-6) in comparison to HC. Longitudinally, we observed higher GCIP thinning in Eye^ON- than in HC (annual loss -0.0042 mm³, p = 0.044). VA did not change longitudinally.
Conclusions: Our results suggest GCIP loss independent of clinical attacks in AQP4-IgG seropositive NMOSD. Potential explanations of GCIP thinning include an AQP4-IgG induced primary retinopathy, drug-induced neurodegeneration and retrograde neuro-axonal degeneration from attack- or lesion-related damage as well as from a chronic optic neuropathy. Further studies are needed to investigate if targeting a progressive retinopathy is relevant for NMOSD diagnosis and treatment.
Disclosure: The project was supported with grants from the German Ministry for Education and Research (BMBF/KKNMS; Competence Network Multiple Sclerosis (to FP, KR), from the Deutsche Forschungsgemeinschaft (DFG, grant Exc. 257 to FP, AUB), from the National Multiple Sclerosis Society (to FP), from the Guthy-Jackson Charitable Foundation (to FP, AUB) and from Novartis (to HZ). FCO is employee of Nocturne UG, unrelated to this work. JH reports a grant for OCT research from the Friedrich-Baur-Stiftung, personal fees and non-financial support from Merck, grants, personal fees and non-financial support from Novartis, personal fees from Roche, non-financial support from Bayer Healthcare, personal fees from Santhera, personal fees and non-financial support from Biogen, personal fees and non-financial support from Sanofi Genzyme, non-financial support of the Guthy-Jackson Charitable Foundation, all outside the submitted work. ARF is sponsored by Abide Therapeutic outside of the submitted work and reports no potential conflicts of interest. NL has nothing to disclose. HZ reports grants from Novartis, during the conduct of the study. SM has nothing to disclose; he is named as inventor on a patent application describing OCT image analysis. NB has nothing to disclose. JBS received speaking fees and travel grants from Bayer Healthcare, sanofi-aventis/Genzyme, Biogen and Teva Pharmaceuticals, unrelated to the present scientific work. PA reports grants, personal fees and non-financial support from Allergan, personal fees and non-financial support from Bayer Healthcare, grants, personal fees and non-financial support from Biogen, grants, personal fees and non-financial support from Ipsen, grants, personal fees and non-financial support from Merz Pharmaceuticals, personal fees and non-financial support from Merck, grants, personal fees and non-financial support from Novartis, non-financial support from Sanofi-Aventis/Genzyme, personal fees and non-financial support from Teva, grants, personal fees and non-financial support from Roche, outside the submitted work. KR reports research support Novartis and Merck Serono as well as speaking fees or travel grants from Bayer Healthcare, Biogen Idec, Merck Serono, sanofi-aventis/Genzyme, Teva Pharmaceuticals, Roche, Novartis and the Guthy-Jackson Charitable Foundation, all unrelated to this work. TK received travel expenses and personal compensations from Bayer Healthcare, Teva Pharma, Merck, Novartis Pharma, Sanofi-Aventis/Genzyme, Roche and Biogen as well as grant support from Bayer-Schering AG, Novartis and Chugai Pharma, unrelated to this work. OW has nothing to disclose. SJ has nothing to disclose. MIL and JP were funded for highly specialized service for neuromyelitis optica - NHS, UK, grants. JP also received research support from the MS society and Guthy-Jackson Charitable Foundation. MIL further reports personal fees from Biogen Idec and grants from Novartis, outside the submitted work. JP reports grants and personal fees from Merck Serono, grants and personal fees from Biogen Idec, personal fees from Teva, grants from Chugai, grants and personal fees from MedImmun, grants and personal fees from Alexion, grants and personal fees from Novartis, personal fees from Roche, grants from Genzyme, grants and personal fees from ABIDE, personal fees from TG Therapeutics, outside the submitted work. In addition, JP has a patent Isis: Diagnosing Multiple Sclerosis. FP reports research grants and speaker honoraria from Bayer, Teva, Genzyme, Merck, Novartis, MedImmune and is member of the steering committee of the OCTIMS study (Novartis), all unrelated to this work. AUB is founder and holds shares of Motognosis and Nocturne UG. He is named as inventor on several patent applications describing serum biomarkers for MS, perceptive visual computing for tracking of motor dysfunction and OCT image analysis.