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

Abstract

 

Purpose

 

To calculate Physiologic Inter-eye Percent Difference (PIPD) values¹ for LC Beam Diameter (BD), Pore Diameter (PD), Connective Tissue Volume Fraction (CTVF), Connective Tissue Volume (CTV) and Laminar Volume (LV) within 12 central and 12 peripheral sub-sectors and within inner, middle and outer laminar depths of 4 Bilateral Normal (BN) NHPs and compare them to EG vs Control eye differences within 17 NHP sacrificed at the onset of early EG (0-30% axon loss).^2,3

 

Methods

 

ONHs underwent 3D reconstruction^1,3 and LC beam segmentation.⁴ Each beam and pore voxel were assigned a diameter based on the largest sphere that contained it before being transformed to one of twelve 30° sectors in a common cylinder. All data were converted to right eye orientation. Mean BD, PD, CTVF, CTV, and LV within 12 central and 12 peripheral sub-sectors and within inner, middle and outer laminar depths were calculated. PIPD_max values for each parameter were defined¹ to be the maximum value of their range within the 4 BN NHPs. Eye-specific PIPD_max change (Fig 1) and Frequency of Change maps (Fig 2) were generated by Sector, Sub-sector and Depth for each parameter.

 

Results

 

PIPD_max values were substantial, requiring EG vs Control eye differences ranging from 4 to 96% to achieve PIPD_max change criteria. Fig. 1 demonstrates PIPD_max increases in BD in 13 eyes, PD in 16 eyes, CTV in 15 eyes and LV in 17 eyes. A minority of EG eyes demonstrated reductions (5, 7, 2, and 5 eyes, respectively) as well. CTVF change occurred less frequently (12 eyes) and involved decreases (9 eyes) as well as increases (6 eyes). BD increases were most common within the superior temporal and inferior nasal sectors (Fig 2). This contrasted with PD and CTV in which superior nasal and inferior temporal increases predominated. BD, PD and LV increases were more common peripherally than centrally. LMA change by depth was variable depending upon the parameter (Fig 2) and eye (Fig 1).

 

Conclusions

 

Eye-specific laminar remodeling occurs early in the NHP ONH response to chronic IOP elevation. The relationships between LMA remodeling, longitudinal SDOCT ONH and RNFLT change and axon loss are under study in a subset of these eyes.²<br /> ¹Yang H, et al. IOVS 2009;50:224-234<br /> ²He L, et al. IOVS 2014;55:574-586<br /> ³Yang H, et al. IOVS 2011;52:345-363<br /> ⁴Grau V, et al. IEEE Trans Med Imaging 2006;25:245-255