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Multicenter Study
. 2020 Dec 1;138(12):1264-1271.
doi: 10.1001/jamaophthalmol.2020.4242.

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

Vivek Vijay  1   2   3 , Susan P Mollan  4 , James L Mitchell  1   2   3 , Edward Bilton  4 , Zerin Alimajstorovic  1 , Keira A Markey  1   3 , Anthony Fong  4   5 , Jessica K Walker  4 , Hannah S Lyons  4 , Andreas Yiangou  1   2   3 , Georgios Tsermoulas  6 , Kristian Brock  7 , Alexandra J Sinclair  1   2   3
Affiliations
Multicenter Study

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

Vivek Vijay et al. JAMA Ophthalmol. .

Abstract

Importance: 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.

Objective: To determine whether OCT of the optic nerve head in papilledema could act as a surrogate measure of ICP.

Design, setting, and participants: 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.

Main outcomes and measures: 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.

Results: 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).

Conclusions and relevance: 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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Mollan reported personal fees from Heidelberg Engineering and advisory board fees from Invex Therapeutics during the conduct of the study and personal fees from Allergan, Santen, Sathera, Roche, Chugai, and Novartis outside the submitted work. Dr Mitchell reported grants from Ministry of Defence during the conduct of the study. Dr Brock reported personal fees from Invex Therapeutics during the conduct of the study; and equity ownership in AstraZeneca and GlaxoSmithKline, personal fees from Eli Lilly reimbursement of costs from Merck and Roche outside the submitted work. Dr Sinclair reported fees from Invex Therapeutics as a company director with salary and stock options during the conduct of this study; and personal fees from Novartis and Allergan outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Distribution of Retinal Nerve Fiber Layer (RNFL) and Optical Nerve Head Central Thickness (ONH CT) Values per Frisén Grade and Correlation of Telemetric Intracranial Pressure (ICP) With RNFL and ONH CT
A and B, Box-and-whisker plots showing medians, ranges, and interquartile ranges (IQRs) of RNFL thickness (A) and ONH CT (B) per Frisén grade, with medians (IQRs) documented numerically for each Frisén grade. C and D, Scatterplots of the mean telemetric ICP values (seated) and optic nerve head central thickness values. Optic nerve head CT is significantly correlated with ICP (B, right eye: r = 0.60; P = .02; C, left eye, r = 0.73; P = .002). pRNFL indicates peripapillary retinal nerve fiber layer.
Figure 2.
Figure 2.. Bootstrap Surrogacy Analysis of Intracranial Pressure (ICP) and Optical Coherence Tomography (OCT) Outcomes
The x-axis reflects changes in OCT with change in ICP on the y-axis. The lines are simple linear regressions, and the shaded regions are 95% CIs of the mean. Changes in ICP are plotted at 3, 12, and 24 months. Each positive value represents improvement (ie, reduction in ICP and OCT); the larger the angle of the slope, the greater the association. A, Optical nerve head central thickness (CT) on the y-axis with a positive association between parameters observed over the time horizons. B, Retinal nerve fiber layer (RNFL) on the y-axis with seemingly random dispersion of data points, indicating a lack of association between retinal nerve fiber layer and ICP.
See this image and copyright information in PMC

References

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