Tortuous Pore Path Through the Glaucomatous Lamina Cribrosa

Bo Wang,James G Fujimoto,Katie A Lucy,Jonathan Liu,Zachary Nadler,Larry Kagemann,Chen Lu,Ireneusz Grulkowski,Ian A Sigal,Hiroshi Ishikawa,Gadi Wollstein,Richard A Bilonick,Joel S Schuman

doi:10.1038/s41598-018-25645-9

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.

Highlights

The lamina cribrosa (LC) has been identified as one of the primary sites of damage in glaucoma, the second leading cause of blindness worldwide[1]
We investigated the LC pore path in vivo as a surrogate of the ganglion cell axonal pathway
These findings are the first evidence in vivo that the spatial pathway of pores traversing the LC corroborate with histological evidence of distorted axons in glaucomatous eyes

Summary

Introduction

The lamina cribrosa (LC) has been identified as one of the primary sites of damage in glaucoma, the second leading cause of blindness worldwide[1]. These distortions are characterized by increased tortuosity of the axons, which prevent the proper flow Despite this hypothetical mechanism, there have been few studies assessing pore pathways through the LC in vivo[8]. While the limited transverse resolution of conventional OCT (~15–20 μm) does not permit characterization of individual axons, it does allow the characterization of the path of pores which reflects the path of the Center, NYU Langone Health, Department of Ophthalmology, New York University School of Medicine, New York, NY, United States. A number of groups, including ourselves, have published methods of quantifying the LC microstructure, the complex beams and pore that make up the LC, in 3D and in vivo[13,14,15] These automated segmentation algorithms are used to quantify LC microstructure and identify differences between healthy and glaucoma subjects[13,16]. We utilize our single pore tracing analysis to trace and quantify in 3D the individual pores in order to characterize their path through the LC

Objectives

Methods

Results

Conclusion