Ko, Fang; (2019) Findings from retinal optical coherence tomography in a large cohort, UK Biobank. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Background: UK Biobank is a large prospective multi-center community-based study, which included macular optical coherence tomography (OCT) of 67,321 people. OCT is a mainstay of ophthalmic imaging and is a potential screening test for dementia. Aim of research: Cross-sectional analysis examined retinal layers, to determine the range of findings in normal individuals, as well as describe associations with demographic and physiologic variation. Longitudinal analysis assessed associations with not only current cognitive function, but future cognitive decline. Results: All layers showed progressive thinning with older age. As compared to white people, black ethnicity was associated with significantly thicker retinal pigment epithelium (RPE) (+3.35 μm; p<0.001), but thinner photoreceptor inner segment-outer segment (IS-OS), ganglion cell layer-inner plexiform layer complex (GCL-IPL), and macular retinal nerve fibre layer (mRNFL) (-3.76 μm, -4.29 μm, and -3.97 μm, respectively; p<0.001). Higher intraocular pressure was associated with thinner RPE (- 0.04 μm per mmHg, p<0.001), but was not significant at GCL-IPL or mRNFL. Higher body mass index was associated with thinner photoreceptor IS-OS (-0.12 μm per kg/m2, p<0.001). Asian and Chinese ethnicity, refractive error, height, sex, smoking, and blood pressure showed mixed results. Socioeconomic deprivation, educational levels, and cognitive function were examined for GCL-IPL and mRNFL. Socioeconomic deprivation was associated with significantly thinner GCL-IPL, but was not significant at mRNFL. In contrast, lower education was significantly associated with thinner mRNFL but was not significant at GCL-IPL. Thinner mRNFL was associated with worse baseline cognitive performance. Follow-up cognitive tests were performed for 1251 participants. Participants with mRNFL thickness in the two thinnest quintiles were almost twice as likely to have at least one test score worse at follow-up cognitive testing (quintile 1: odds ratio (OR) 1.92, 95% CI: 1.29, 2.85, p<0.001, quintile 2: OR: 2.08, 95% CI: 1.40, 3.08, P< 0.001). While there were some associations between GCL-IPL and baseline cognitive function, no association was detected for risk of future cognitive decline. Significance: Retinal thickness is variable and dynamic. This work will inform interpretation of both past and future research, as physiologic and demographic variation is associated with thickness of each layer. Of note, I show an association between IOP and RPE but not mRNFL. Further, thinner mRNFL is associated with greater likelihood of cognitive decline in the future. These observations have implications for future research, as well as prevention and treatment of dementia.

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