Abstract
Abstract: :
Purpose: To characterize plastic deformation of the lamina cribrosa within high-resolution, digital, 3D reconstructions of early-glaucoma (EG) monkey optic nerve heads (ONHs) perfusion-fixed at an intraocular pressure (IOP) of 10 mm Hg. Methods: Both eyes of three monkeys (one eye given a laser-induced IOP elevation then followed to the onset of CSLT-detected ONH surface change) were set to an IOP of 10 mm Hg for 60 minutes, then each monkey was perfusion-fixed. Fixing the EG eye at 10 mm Hg isolates the plastic (permanent) deformation in the load-bearing tissues. The trephinated ONH and peripapillary sclera from each eye was embedded in paraffin, and microtome serial sectioned at 3 µm thickness, with the embedded tissue block face stained and imaged after each cut. The images were then aligned, and the scleral canal wall, sclera, Border Tissue of Elschnig, Bruch's membrane, lamina cribrosa, optic nerve septa, pial sheath, and vasculature were delineated as unique objects. The delineated images were then stacked (creating 2.5x2.5x3 µm voxels), color mapped, and volume rendered (OpenDX software). Custom software was employed to simultaneously view serial 5 µm sagittal (along both the superior-inferior and nasal-temporal axes), and transverse sections of the voxel geometry of both eyes of each monkey, which allowed for direct comparison of the load-bearing tissues in the 3D reconstructions of contralateral eyes. Results: In all three monkeys, profound plastic posterior deformation of the central lamina cribrosa is evident within the EG (compared to its contralateral normal) ONHs. Peripherally, laminar deformation beneath Bruch's membrane was greatest inferiorly in all three EG eyes, however in 2 of the 3 eyes, mild to moderate excavation was present in all four quadrants. In one monkey, profound thinning of the peripapillary sclera was present in the EG eye. Peripheral plastic posterior deformation of the lamina was much greater in the two EG eyes with oblique optic nerve insertions and thin peripapillary sclera, compared to the one EG eye with a straight-sided scleral canal. Conclusions: Within the geometries of 3 early-glaucoma monkey ONHs, perfusion-fixed at IOP 10 mm Hg, profound posterior plastic deformation in the lamina cribrosa is present at the onset of CSLT-detected ONH surface change. These data support our hypothesis that the connective tissues of the ONH are damaged early in glaucoma and suggest that while the inferior quadrant may be most susceptible, permanent connective tissue deformation in all 4 quadrants can be present early in the disease.
Keywords: optic disc • intraocular pressure • imaging/image analysis: non-clinical