Background: The diagnosis of multiple sclerosis (MS) is based on a combination of clinical and para-clinical tests. The potential contribution of retinal optical coherence tomography (OCT) has been recognised. We tested the feasibility of OCT measures of retinal asymmetry as a diagnostic test for MS at the community level. Method: In this community based study on 62,180 subjects we examined the diagnostic potential of the inter-eye difference of inner retinal OCT data for MS using the UK Biobank data collected at 22 sites between 2007-2010. The APOSTEL guidelines were followed for reporting automated retinal layer segmentation data and quality control. The inter-eye percentage difference (IEPD) and inter-eye absolute difference (IEAD) were calculated for the macular retinal nerve fibre layer (mRNFL), ganglion-cell inner plexiform layer complex (mGCIPL) and ganglion cell complex (mGCC). Area under the receiver operating characteristic curve (AUC) comparisons were followed by univariate and multivariable comparisons accounting for a large range of diseases and comorbidities. Cutoff levels were optimised by ROC and the Youden index. Findings: The prevalence of MS was 0.0027 (95%CI 0.0023-0.0031). Overall the discriminatory power of diagnosing MS with the IEPD (AUC 0.71, 95%CI 0.67-0.76) and IEAD (0.71, 95%CI 0.66-0.75) for the mGCIPL were significantly higher if compared to the mGCC (IEPD AUC 0.66, 95%CI 0.62-0.71, p<0.05; IEAD AUC 0.64, 95%CI 0.60-0.68, p<0.001) and mRNFL (IEPD AUC 0.58, 95%CI 0.54-0.62, p<0.0001; IEAD AUC 0.54, 95%CI 0.50-0.58, p<0.0001). Screening sensitivity levels for the mGCIPL IEPD (4% cut-off) were 91.5% and for the IEAD (4 μm cut-off) 92.1%. Specificity levels were 18.3% and 17.3%. The number of comorbidities was important. There was a stepwise decrease of the AUC from 0.74 in healthy controls to 0.65 in more than nine comorbidities. In the multivariable analyses greater age, diabetes mellitus and a non-white ethnic background were relevant confounders. Interpretation: The OCT GCIPL IEPD and IEAD should be considered as a supportive measurements for MS diagnostic criteria in a young person without relevant co-morbidity. Retinal OCT imaging is accurate, rapid, non-invasive, widely available and may therefore help to reduce need for invasive and more costly procedures. To be viable, higher sensitivity and specificity levels are needed. This may be achieved with artificial intelligence-based approaches incorporating inter-eye retinal asymmetry. Funding Statement: The NIHR BRC at Moorfields Eye Hospital supported AP, NGS, PAK, PTK, PJF, and PJP. This analysis was supported by the Eranda Foundation via the International Glaucoma Association, UCL ORS & GRS programmes. PJF received support from the Richard Desmond Charitable Trust, via Fight for Sight, London. Declaration of Interests: AP reports personal fees from Novartis, Heidelberg Engenieering, Zeiss, grants from Novartis, outside the submitted work; and AP is part of the steering committee of the OCTiMS study which is sponsored by Novartis. AP is part of the steering committee of Angio-OCT which is sponsored by Zeiss. PAK reports personal fees from Allergan, personal fees from Topcon, personal fees from Heidelberg Engineering, personal fees from Haag-Streit, personal fees from Novartis, personal fees from Bayer, personal fees from Optos, personal fees from DeepMind, grants from National Institute for Health Research (NIHR), outside the submitted work. CR reports employment by Topcon Healthcare Solutions Inc., outside submitted work. NGS has nothing to disclose. PJF reports personal fees from Allergan, Carl Zeiss, Google/DeepMind and Santen, a grant from Alcon, outside the submitted work; PJP reports grants from Topcon Inc, outside the submitted work. All other authors declare no conflicts of interest. Ethics Approval Statement: The North West Multi-center Research Ethics Committee approved the study (reference no., 06/MRE08/65), in accordance with the tenets of the Declaration of Helsinki. Detailed information about the study is available at the UK Biobank web site (www.ukbiobank.ac.uk).