Tortuous Pore Path Through the Glaucomatous Lamina Cribrosa

Abstract

The lamina cribrosa is a primary site of damage in glaucoma. While mechanical distortion is hypothesized to cause reduction of axoplasmic flow, little is known about how the pores, which contains the retinal ganglion cell axons, traverse the lamina cribrosa. We investigated lamina cribrosa pore paths in vivo to quantify differences in tortuosity of pore paths between healthy and glaucomatous eyes. We imaged 16 healthy, 23 glaucoma suspect and 48 glaucomatous eyes from 70 subjects using a swept source optical coherence tomography system. The lamina cribrosa pores were automatically segmented using a previously described segmentation algorithm. Individual pore paths were automatically tracked through the depth of the lamina cribrosa using custom software. Pore path convergence to the optic nerve center and tortuosity was quantified for each eye. We found that lamina cribrosa pore pathways traverse the lamina cribrosa closer to the optic nerve center along the depth of the lamina cribrosa regardless of disease severity or diagnostic category. In addition, pores of glaucoma eyes take a more tortuous path through the lamina cribrosa compared to those of healthy eyes, suggesting a potential mechanism for reduction of axoplasmic flow in glaucoma.

Figure 1

Pore path tracing. (A) Enface view of the lamina cribrosa. (B) Pore paths were traced with respect to depth via the centroid of the segmented pores. (C) 3D view of pore path tracing from a subset of pores in a single eye (27 out of 81).

Figure 2

Identification of pore path relative to the disc. (A) Method of identification of pore path relative to the central disc (dotted red line). Positive distance change (path 1; blue) indicated convergence towards the center, while negative distance change (path 2; green) indicated convergence away from the center. (B) Example of LC identified to have pores going towards the disc center (red dotted line) and (C) away from disc center.

Figure 3

Assessment of pore path relative to disc. (A) Schematic demonstration of examples of negative path change (pores move away from disc center going from anterior to posterior) and positive path change (pores move towards the disc center). (B) Boxplot of pore path change with respect to diagnosis (H – healthy, GS – glaucoma suspect, GL – glaucomatous eyes) and (C) visual field mean deviation.

Figure 4

Assessment of pore tortuosity. (A) Pore tortuosity was defined by dividing the distance traveled by the pore centroid (yellow line) by the shortest distance between the top and bottom pore (purple line). (B) Schematic showing examples of low tortuosity (green) and high tortuosity (red). (C) Boxplot of tortuosity as a function of diagnosis (H – healthy, GS – glaucoma suspect, GL – glaucomatous eyes). (D) Probability density distribution of pore tortuosity as a function of disease (Green – healthy, Blue – glaucoma suspect, Red – glaucomatous eyes). (E) Pore tortuosity as a function of visual field mean deviation, with the green lines denoting the 95% confidence interval of the healthy subjects.