BACKGROUND: Epigenetic variation is implicated in a range of non-communicable diseases, including those of the eye. However, investigating the role of epigenetic variation in ocular disease remains problematic as the degree of correlation in epigenetic profile between central (such as the brain or eye) and peripheral tissues (blood or saliva) within an individual remains largely unclear. METHODS: Matched whole blood from the subclavian vein, and whole eyes (N=8) were obtained post-mortem. DNA was isolated from blood, neurosensory retina, retinal pigment epithelium (RPE)/choroid and optic nerve tissue. DNA methylation profiling was performed using the Illumina Infinium HumanMethylation450 platform. Following standard quality control measures a total of 433,768 methylation values common to all samples were available for use in subsequent analysis. RESULTS: Unsupervised hierarchical clustering and principal components analysis revealed tissue of origin as the main driver of variation within the dataset. Despite this, there was a strong correlation of methylation profiles between tissues within each individual. Over 255,000 CpG sites were found to have similar methylation levels (beta <0.2 or beta >0.8) across different tissues in the same individuals, with a further ~16,000 sites having similar methylation profiles across ocular tissues only. Only a small proportion of probes showing interindividual variation in blood, covaried across blood and eye tissues within individuals. CONCLUSIONS: An improved understanding of the epigenetic landscape of the eye will have important ramifications for regenerative medicine and ongoing dissection of gene-environment interactions in eye disease. Despite a generally high correlation in methylation values irrespective ofsample origin, tissue type is the major driver of methylation variation, with only limited covariation between blood and any specific ocular tissue. Caution is warranted when aiming to infer ocular tissue methylation status from blood samples.