Overall Lamina Cribrosa (LC) Microarchitectural (LMA) Change in Non-Human Primate (NHP) Early Experimental Glaucoma (EG) by Region

Abstract

 

Purpose

 

To compare EG vs Control Eye differences in LC Beam Diameter (BD), Pore Diameter (PD), Connective Tissue Volume Fraction (CTVF), Connective Tissue Volume (CTV) and Laminar Volume (LV) within 17 NHPs^1,2 at the onset of unilateral EG within 12 central and 12 peripheral sub-sectors and within inner, middle and outer laminar layers.

 

Methods

 

ONHs underwent 3D reconstruction^2,3 and LC beam segmentation.⁴ Each beam and pore voxel was assigned a diameter based on the largest sphere that contained it before transformation to one of twelve 30° sectors in a common cylinder. All data were converted to right eye orientation and mean BD, PD, CTVF, CTV and LV was calculated within each region. Sectoral, Sub-sectoral and depth effects were assessed for each parameter by analysis of variance (ANOVA) using General Estimating Equations (GEE). EG vs Control eye differences were assessed using GEE.

 

Results

 

EG effects were significant for BD (Control 19.5 vs EG 20.6 µm, p=0.03), CTV (Control 83 vs EG 11710⁶µm³, p<0.0001) and LV (Control 180 vs EG 27210⁶µm³, p<0.0001) (Table 1). Significant interactions (p<0.05) included: EGSector (all parameters), EGSub-sector (PD), EGDepth (CTVF). EG eye PD increased significantly more in peripheral (10.2% ± 20.3%) than central (3.0% ± 15.0%) sub-sectors. Sectoral (Fig 1A) and subsector (Fig 1B) analyses suggest BD increases were greatest inferior nasally for all laminar depths and that peripheral change was greater than central change for regions of BV, PD and CTVF. CTV and LV behaved similarly, increasing in the majority of sectors except within the peripheral subsectors of the inferior-temporal inner layer and nasally in the middle and outer layers.

 

Conclusions

 

BD, CTV and LV increase in response to early chronic IOP elevation in the NHP eye and these increases are different by sector and sub-sector. While overall changes in CTVF are minimal, substantial sectoral and depth changes occur but in opposing directions. The mechanisms underlying regional LMA change in NHP early EG and their contributions to axonal injury are under active study. ¹He L, et al. IOVS 2014;55:574-586; ²Yang H, et al. IOVS 2011;52:345-363; ³Yang H, et al. IOVS 2009;50:224-234; ⁴Grau V, et al. IEEE Trans Med Imaging 2006;25:245-255