Structural Characterization of Human Lamina Cribrosa and Its Correlation to IOP-induced Strain

Abstract

Purpose : To characterize the collagen beam network microstructure of the human lamina cribrosa (LC), its regional variations, and correlation with strains.

Methods : 10 human eyes ranging from 26 - 93 years old were subjected to ex vivo inflation testing and morphological characterization. The posterior scleral shell was excised from the globe and mounted in an inflation chamber, while the LC of the optic nerve head (ONH) was imaged by a Zeiss 710 laser scanning microscope using second harmonic generation (SHG) (Midgett et al. 2017). The mounted scleral shell was subjected to acute IOP elevation from 5mmHg to 45mmHg, controlled by a manometer. This inflation test yielded a 3D deformation and strain field (Fig 1f) using digital volume correlation (DVC). Next, a Huygens Essential deconvolution algorithm and a modified Frangi filter algorithm (Campbell et al. 2015) were used to reduce noise and enhance contrast of the SHG image stacks (Fig 1a-c). A custom morphological algorithm was developed to extract 9 structural parameters, including the degree of anisotropy of collagen beams, pore areal density, density of beam junctions (Fig 1e), and beam width, aspect ratio, and tortuosity. The maximum principal strain, maximum shear strains, and all structural parameters were average over 8 anatomical regions (Fig 1d). Variations in structural outcomes with region, age, and strains were analyzed using a linear mixed model.

Results : Preliminary results showed significant variations between central and peripheral regions in density of beam junctions, connectivity, tortuosity and pore density (Fig 2a). The maximum principal strain increased with the pore area fraction (p=0.024) and beam tortuosity (p=0.005), but decrease with the beam connectivity (p=0.018) (Fig 2b-d).

Conclusions : Variations in the LC collagen network structure within the optic nerve head correlate with tensile and shear strains and may be predictive of the susceptibility and progression of glaucomatous axonal damage.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.