Fig 1.
(A) Diagram of the experimental setup. Intraocular pressure (IOP) and intracranial pressure (ICP) were controlled using a gravity-based perfusion system. OCT imaging of the lamina cribrosa (LC) (red box) was performed after altering IOP and/or ICP. (B) A sagittal slice of the OCT volume. White dotted line denotes the plane of the (C) enface view of the ONH. (D) At every given ICP, IOP was altered and the ONH was imaged after allowing the tissue to stabilize for 5 minutes at every IOP condition. After completing all IOP conditions, a new ICP was set and the IOP conditions repeated.
Fig 2.
(A) Images were adjusted for isotropic dimensions, (B) and rotated to match the angle of Bruch membrane opening (BMO). (C) Images were translated in the axial direction to match the axial height of the BMO. (D) The microstructures were aligned manually via 3D rotation and translation. (E) Visible LC was denoted and a common overlapping region (white color region) was used for analysis.
Table 1.
Comparison of the various models that were tested.
Lower Akaike information criterion (AIC) denotes the better model. * denotes interaction term between the variables. Bold denotes best performing model as judged by AIC.
Fig 3.
Example of variations in lamina cribrosa (LC) microstructure with pressure modulation.
(A) enface images show variation in the vasculature (red arrows) with differences in intracranial pressure. (B) Matching regions of the LC also feature prominent changes in LC microstructure, with decreased pore diameter and beam thickening observed with higher intracranial pressure (ICP; right), at a fixed intraocular pressure (IOP).
Fig 4.
Matching LC microstructure between enface OCT images (left column) and histology (right column).
Color lines and arrow (bottom row) were added to illustrate some of the corresponding ONH structures. Note the similarity in structures discernible with both techniques, including the details of collagen beams and pores of the LC.
Fig 5.
Change in lamina cribrosa (LC) beam thickness with intraocular (IOP) and intracranial pressure (ICP).
(A) Contour plot showing change in beam thickness as a function of IOP and ICP. Black lines indicate the contour line at the same beam thickness. Blue dots indicate actual measurements acquired in the experiments. A sample of the contour plot at a set of (B) fixed ICP (ICP = 10mmHg, brown line; ICP = 35mmHg, dark green) and (C) fixed IOP (IOP = 10mmHg, purple; IOP = 45mmHg, light blue) conditions demonstrate the complex interaction between IOP and ICP on beam thickness.
Fig 6.
Change in lamina cribrosa (LC) pore diameter with intraocular (IOP) and intracranial (ICP) pressure.
(A) Contour plot showing change in beam pore ratio as a function of IOP and ICP. Black lines indicate the contour line at the same pore diameter. Blue dots indicate actual measurements acquired in the experiments. A sample of the contour plot at a set of (B) fixed ICP (ICP = 10mmHg, brown line; ICP = 35mmHg, dark green) and (C) fixed IOP (IOP = 10mmHg, purple; IOP = 45mmHg, light blue) conditions demonstrate the complex interaction between IOP and ICP on pore diameter.
Fig 7.
Change in lamina cribrosa (LC) beam thickness to pore diameter ratio with intraocular (IOP) and intracranial (ICP) pressure.
(A) Contour plot showing change in beam pore ratio as a function of IOP and ICP. Black lines indicate the contour line at the same beam thickness to pore diameter ratio. Blue dots indicate actual measurements acquired in the experiments. A sample of the contour plot at a set of (B) fixed ICP (ICP = 10mmHg, brown line; ICP = 35mmHg, dark green) and (C) fixed IOP (IOP = 10mmHg, purple; IOP = 45mmHg, light blue) conditions demonstrate the complex interaction between IOP and ICP on beam pore ratio.
Fig 8.
Monkey specific response to pressure modulation.
Scatterplot of beam thickness, pore diameter, and beam thickness to pore diameter ratio versus translaminar pressure difference (TLPD) for the 5 monkeys (color-coded). Each line indicated the line of best fit to help illustrate the trend.