Association Between Peripapillary Bruch's Membrane Shape and Intracranial Pressure: Effect of Image Acquisition Pattern and Image Analysis Method, a Preliminary Study

Abstract

Background/Aims: High intracranial pressure (ICP) is associated with changes in peripapillary Bruch's membrane (pBM) shape on optical coherence tomography (OCT) images of the optic nerve head. It is not known if image acquisition pattern and analysis method impact this association.Materials and Methods: Cross sectional OCT scans of the optic nerve head were obtained at six angles using a radial scan pattern in 21 subjects immediately prior to ICP measurement via lumbar puncture. On each image, Bruch's membrane was manually segmented and defined by either 14 or 16 semi-landmarks and either rater identified, or distance identified boundaries. For each of these four image analysis strategies, geometric morphometric analysis identified the first principal component of Bruch's membrane shape for all images and for the set of images taken at each angle. Repeated measures ANOVA of the first principal component magnitude (PC1) for all images assessed for shape difference between image angles. Linear generalized estimating equation models assessed association between angle specific first principal component magnitudes (PC1) and ICP for each angle. Receiver operating characteristic analysis assessed angle specific PC1s' ability to differentiate elevated from normal ICP.Results: The first principal component represented deflection into the vitreous for all scan angles, but quantitatively differed across scan angles (p < 0.005, repeated measures ANOVA). Angle specific first principal components were positively correlated with ICP (p < 0.005 for all angles, generalized estimating equation models). All angle specific first principal components showed excellent ability to classify ICP (area under curve ≥ 0.8 for all). These results were independent from image analysis strategy.Discussion: Though qualitative changes in Bruch's membrane shape are similar regardless of cross-sectional angle of the 2-D OCT scan, they differ quantitatively between OCT scan angles, meaning that pBM is not axially symmetric and therefore PC1 extracted from different 2-D scan angles can't be compared between individuals. However, we do not identify an optimal scan angle for classification of ICP since there is a similarly strong linear relationship between the first principal component of shape and ICP and angle specific first principal components of Bruch's membrane shape showed similarly excellent ability to differentiate elevated from normal ICP. The results support development of Bruch's membrane shape extracted from 2-D cross sectional optic nerve head OCT scans as a biomarker of ICP and emphasize the importance of consistency of scan angle. This is relevant for developing diagnostic protocols that use OCT to detect high ICP states.

Three-Dimensional Characterization of Peripapillary Retinal Pigment Epithelium-Basement Membrane Layer in Patients following Lumbar Puncture

“…The magnitude of Γ varied significantly across different radial directions both before and after the LP (Figure 7). This is consistent with the observation by Malhotra et al, who found that the ppRPE/BM shape before LP was different along different radial directions [15]. However, the ppRPE/BM layer angle changes following the LP did not vary significantly along different radial directions.…”

“…Moreover, only one OCT scan per patient was used for the ppRPE/BM layer shape analysis (mostly the temporal-nasal scan) [9][10][11]14] due to the labor intensive methods for manual segmentations. However, one recent study showed that the ppRPE/BM layer shapes were different across various radial directions [15]. A three-dimensional (3D) characterizations of the ppRPE/BM layer is needed for better mechanistic understanding of ONH morphology following ICP changes [16].…”

Methods for Quantifying Optic Disc Volume and Peripapillary Deflection Volume Using Radial Optical Coherence Tomography Scans and Association With Intracranial Pressure

“…BMDV is an attractive marker of ICP since it is thought to reflect a direct mechanical result of elevated ICP on the posterior globe. Prior studies have demonstrated associations between high ICP and BM deflection into the eye using 2-D shape analysis of OCT and surface topography of MRI (6, 9, 18, 19) 3-D shape analysis applied to OCT demonstrated resolution of BM deflection within individuals undergoing ICP treatment over months (5) and 2-D shape analysis demonstrated detectable changes in hours following ICP lowering (9). Though changes in BMDV and ONHV were moderately correlated in our study, they may have distinct clinical roles as suggested by a previous longitudinal analysis demonstrating decoupling between BM shape and ONHV (5).…”

“…Patients scheduled to undergo an LP for clinical reasons were recruited from the University of Illinois at Chicago ophthalmology and neurology clinics between November 2014 and March 2016 to participate in a study of ophthalmic manifestations of high ICP, other results of which have been reported separately (6, 9, 10). The research adhered to the tenets of the Declaration of Helsinki and was approved by the University of Illinois at Chicago Institutional Review Board.…”

“…Excluding the region prone to artifact from analysis has been demonstrated to have minimal impact on the relationship between ICP and two dimensional pBM shape (6). However, the use of two dimensional analysis to represent this three dimensional structure in high ICP states may not be appropriate since pBM is not radially symmetric and two dimensional scan angle impacts the ICP-pBM shape relationship (6, 8). To address this we have developed a method for three dimensional ONHV and pBMDV using OCT B-scans acquired in a radial pattern.…”