Associations Between Circulating Polyunsaturated Fatty Acids and Photoreceptor Measurement

Purpose: Polyunsaturated fatty acids (PUFAs) are enriched in the retina and may play essential roles in photoreceptor microstructure. This study aimed to investigate associations between circulating omega-3 and omega-6 fatty acid-related measures and photoreceptor inner and outer segment thickness assessed by optical coherence tomography (OCT) in the UK Biobank. Methods: In this cross-sectional association study, circulating omega-3 and omega-6 fatty acid-related measures were quantified using a nuclear magnetic resonance metabolomics platform. Photoreceptor inner segment (IS) and outer segment (OS) thicknesses were measured by spectral-domain OCT obtained during the same baseline assessment period. β coefficients with 95% confidence intervals (CIs) were estimated using linear regression models adjusted for covariates. Restricted cubic spline analyses were performed to assess dose-response relationships, and subgroup analyses examined potential interaction effects. Results: Higher circulating levels of omega-3 fatty acids were associated with a thinner IS layer (β = -0.059; 95% CI, -0.096 to -0.022; P = 0.002), whereas higher omega-6 fatty acid levels were linked to a thinner OS layer (β = -0.229; 95% CI, -0.338 to -0.121; P < 0.001). These relationships were largely linear within the physiological range. Subgroup analyses indicated that ethnicity modified the association with OS thickness. Conclusions: Circulating omega-3 and omega-6 fatty acid-related measures were differentially associated with photoreceptor inner and OS thickness measured by OCT, with omega-3-related indices generally associated with thinner ISs and thicker OSs and omega-6-related indices showing opposite patterns. Translational Relevance: Maintaining a favorable PUFAs balance may be beneficial for photoreceptor microstructure.