Bianchi A, Cortese R, Prados F, Tur C, Kanber B, Yiannakas MC, Samson R, De Angelis F, Magnollay L, Jacob A, Brownlee W, Trip A, Nicholas R, Hacohen Y, Barkhof F, Ciccarelli O, and Toosy AT
Background: Optic neuritis (ON) is a common feature of inflammatory demyelinating diseases (IDDs) such as multiple sclerosis (MS), aquaporin 4-antibody neuromyelitis optica spectrum disorder (AQP4 + NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). However, the involvement of the optic chiasm (OC) in IDD has not been fully investigated., Aims: To examine OC differences in non-acute IDD patients with (ON+) and without ON (ON-) using magnetisation transfer ratio (MTR), to compare differences between MS, AQP4 + NMOSD and MOGAD and understand their associations with other neuro-ophthalmological markers., Methods: Twenty-eight relapsing-remitting multiple sclerosis (RRMS), 24 AQP4 + NMOSD, 28 MOGAD patients and 32 healthy controls (HCs) underwent clinical evaluation, MRI and optical coherence tomography (OCT) scan. Multivariable linear regression models were applied., Results: ON + IDD patients showed lower OC MTR than HCs (28.87 ± 4.58 vs 31.65 ± 4.93; p = 0.004). When compared with HCs, lower OC MTR was found in ON + AQP4 + NMOSD (28.55 ± 4.18 vs 31.65 ± 4.93; p = 0.020) and MOGAD (28.73 ± 4.99 vs 31.65 ± 4.93; p = 0.007) and in ON- AQP4 + NMOSD (28.37 ± 7.27 vs 31.65 ± 4.93; p = 0.035). ON+ RRMS had lower MTR than ON- RRMS (28.87 ± 4.58 vs 30.99 ± 4.76; p = 0.038). Lower OC MTR was associated with higher number of ON (regression coefficient (RC) = -1.15, 95% confidence interval (CI) = -1.819 to -0.490, p = 0.001), worse visual acuity (RC = -0.026, 95% CI = -0.041 to -0.011, p = 0.001) and lower peripapillary retinal nerve fibre layer (pRNFL) thickness (RC = 1.129, 95% CI = 0.199 to 2.059, p = 0.018) when considering the whole IDD group., Conclusion: OC microstructural damage indicates prior ON in IDD and is linked to reduced vision and thinner pRNFL., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: AB has received a research grant from the Italian Society of Neurology; she has been awarded a MAGNIMS-ECTRIMS fellowship in 2023. RC received speaker honoraria/travel support from Roche, Merck Serono, UCB, Sanofi-Genzyme, Novartis, and Janssen, and received a research grant from the Italian Ministry of University and Research. FP received a Guarantors of Brain fellowship 2017-2020. CT is currently being funded by a Miguel Servet contract, awarded by the Instituto de Salud Carlos III (ISCIII), Ministerio de Ciencia e Innovación de España (CP23/00117). She has also received a 2020 Junior Leader La Caixa Fellowship (fellowship code: LCF/BQ/PI20/11760008), awarded by “la Caixa” Foundation (ID 100010434), a 2021 Merck’s Award for the Investigation in MS, awarded by Fundación Merck Salud (Spain), a 2021 Research Grant (PI21/01860) awarded by the ISCIII, Ministerio de Ciencia e Innovación de España, and a FORTALECE research grant (FORT23/00034) also by the ISCIII, Ministerio de Ciencia e Innovación de España. In 2015, she received an ECTRIMS Post-doctoral Research Fellowship and has received funding from the UK MS Society. She is a member of the Editorial Board of Neurology Journal and Multiple Sclerosis Journal. She has also received honoraria from Roche, Novartis, Merck, Immunic Therapeutics, and Bristol Myers Squibb. She is a steering committee member of the O’HAND trial and of the Consensus group on Follow-on DMTs. BK is supported by the NIHR BRC at UCL. FDA has received congress fees or speaker honoraria and/or acted as a consultant for Neurology Academy, Coloplast, Janssen, Merck, Novartis, Roche,Sanofi. WJB has received speaker honoraria and/or acted as a consultant for Biogen, Janssen, Merck, Neuraxpharm, Novartis, Roche, Sanofi, Sandoz and Viatris; he is supported by the NIHR UCLH Biomedical Research Centre. FB is Steering committee or Data Safety Monitoring Board member for Biogen, Merck, ATRI/ACTC and Prothena. He is consultant for Roche, Celltrion, Rewind Therapeutics, Merck, IXICO, Jansen, Combinostics. He has research agreements with Merck, Biogen, GE Healthcare, Roche. Co-founder and shareholder of Queen Square Analytics LTD. OC is a member of independent DSMB for Novartis, gave a teaching talk on McDonald criteria in a Merck local symposium, and contributed to an Advisory Board for Biogen; she is Deputy Editor of Neurology, for which she receives an honorarium. Merck. AD, VC, DW, JS, MCY, and RN have no disclosure. ATT has speaker honoraria from Merck, Biomedia, Sereno Symposia International Foundation, Bayer and At the Limits and meeting expenses from Merck, Biogen Idec and Novartis. Supported by recent grants from the MRC (MR/S026088/1), NIHR BRC (541/CAP/OC/818837) and RoseTrees Trust (A1332 and PGL21/10079). Associate editor for Frontiers in Neurology – Neuro-ophthalmology section and on the editorial board for Neurology and Multiple Sclerosis Journal.