To assess the associations between physiology and demographics, non-ocular pathology and pharmaceutical drug use against peri-papillary retinal nerve fibre layer thickness (pRNFL T) and other optical coherence tomography (OCT) inner retinal measures in normal, healthy eyes. A retrospective, cross-sectional study of 705 consecutive participants with bilateral normal, healthy optic nerves and maculae. PRNFL Ts, vertical cup/disc ratio (CDR), cup volume and macular ganglion cell layer-inner plexiform layer (GCL-IPL) Ts were extracted from Cirrus OCT scans, then regressed against predictor variables of participants' physiology and demographics (eye laterality, refraction, intraocular pressure [IOP], age, sex, race/ethnicity, etc.) and non-ocular pathology and pharmaceutical drug use according to the World Health Organisation classifications. Associations were assessed for statistical significance (p < 0.05) and clinical significance (|β| > 95% limits of agreement for repeated measures). A multitude of non-ocular pathology and pharmaceutical drug use were statistically and clinically significantly associated with deviations in standard OCT inner retinal measures, exceeding the magnitude of other factors such as age, IOP and race/ethnicity. Thinner inner retina and larger optic nerve cup measures were linked to use of systemic corticosteroids, sex hormones/modulators, presence of vasomotor/allergic rhinitis and other diseases and drugs (up to -29.3 [-49.88, -8.72] μm pRNFL T, 0.31 [0.07, 0.54] vertical CDR, 0.29 [0.03, 0.54] mm3 cup volume and -10.18 [-16.62, -3.74] μm macular GCL-IPL T; all p < 0.05). Thicker inner retina and smaller optic nerve cup measures were diffusely associated with use of antineoplastic agents, presence of liver or urinary diseases and other diseases and drugs (up to 67.12 [64.92, 69.31] μm pRNFL T, -0.31 [-0.53, -0.09] vertical CDR, -0.06 [-0.11, 0] mm3 cup volume and 28.84 [14.51, 43.17] μm macular GCL-IPL T; all p < 0.05). There are a multitude of systemic diseases and drugs associated with altered OCT inner retinal measures, with magnitudes far exceeding those of other factors such as age, IOP and race/ethnicity. These systemic factors should at least be considered during OCT assessments to ensure precise interpretation of normal versus pathological inner retinal health.
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