Using Optical Coherence Tomography as a Surrogate of Measurements of Intracranial Pressure in Idiopathic Intracranial Hypertension

Abstract

There is an unmet need for noninvasive biomarkers of intracranial pressure (ICP), which manifests as papilledema that can be quantified by optical coherence tomography (OCT) imaging. To determine whether OCT of the optic nerve head in papilledema could act as a surrogate measure of ICP. This longitudinal cohort study used data collected from 3 randomized clinical trials that were conducted between April 1, 2014, and August 1, 2019. Participants who were female and had active idiopathic intracranial hypertension were enrolled from 5 National Health Service hospitals in the UK. Automated perimetry and OCT imaging were followed immediately by ICP measurement on the same day. Cohort 1 used continuous sitting telemetric ICP monitoring (Raumedic Neurovent P-tel device) on 1 visit. Cohort 2 was evaluated at baseline and after 3, 12, and 24 months and underwent lumbar puncture assessment of ICP. Optical coherence tomography measures of the optic nerve head and macula were correlated with ICP levels, Frisén grading, and perimetric mean deviation. The OCT protocol included peripapillary retinal nerve fiber layer, optic nerve head, and macular volume scans (Spectralis [Heidelberg Engineering]). All scans were validated for quality and resegmented manually when required. A total of 104 women were recruited. Among cohort 1 (n = 15; mean [SD] age, 28.2 [9.4] years), the range of OCT protocols was evaluated, and optic nerve head central thickness was found to be most closely associated with ICP (right eye: r = 0.60; P = .02; left eye: r = 0.73; P = .002). Subsequently, findings from cohort 2 (n = 89; mean [SD] age, 31.8 [7.5] years) confirmed the correlation between central thickness and ICP longitudinally (12 and 24 months). Finally, bootstrap surrogacy analysis noted a positive association between central thickness and change in ICP at all points (eg, at 12 months, a decrease in central thickness of 50 μm was associated with a decrease in ICP of 5 cm H2O). In this study, optic nerve head volume measures on OCT (particularly central thickness) reproducibly correlated with ICP and surrogacy analysis demonstrated its ability to inform ICP changes. These data suggest that OCT has the utility to not only monitor papilledema but also noninvasively prognosticate ICP levels in idiopathic intracranial hypertension.