BackgroundOmega-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have anti-inflammatory and neuroprotective properties. This study sought to determine the relationship between corneal parameters and systemic omega-3 fatty acid levels.MethodsForty-seven participants with no/mild peripheral neuropathy (26 with diabetes and 21 without) underwent comprehensive ocular surface and systemic PUFA assessments. Corneal anatomical parameters were assessed using in vivo confocal microscopy. Corneal sensitivity was measured using non-contact esthesiometry. Relationships between systemic PUFA levels and corneal parameters were evaluated with multiple linear regression, adjusted for age, sex, neuropathy symptom score, and presence of diabetes and dry eye disease. The relationship between corneal nerve fibre length (CNFL) and corneal sensitivity threshold was evaluated.ResultsThe median Omega-3 Index, a measure of erythrocyte EPA and DHA, was 5.21% (interquartile range: 4.44–5.94%) in the study population. Mean ( ± SD) CNFL was 13.53 ± 3.37 mm/mm2. Multiple linear regression showed that Omega-3 Index (β= 0.33;p= 0.02), age (β= −0.46;p= 0.001) and diabetes (β= −0.30;p= 0.03) were independently associated with CNFL (R2= 0.39,p= 0.002). In a separate model, DHA (β= 0.32;p= 0.027) and age (β= −0.41;p= 0.003) were associated with CNFL (R2= 0.37,p= 0.003). Neither systemic EPA nor omega-6 fatty acid levels correlated with CNFL. There was no association between PUFA levels and corneal sensitivity or corneal immune cell density. A negative correlation was found between CNFL and corneal sensation thresholds to a cooled stimulus in diabetes participants, in the central (ρ = −0.50;p= 0.009) and peripheral (ρ = −0.50;p= 0.01) cornea.ConclusionsA positive relationship between the systemic Omega-3 Index and corneal nerve parameters suggests omega-3 PUFA intake may influence corneal nerve architecture.