In-vivo 3D Deformation of Lamina Cribrosa Microstructure in Response to Acute Changes in Intraocular and Cerebrospinal Fluid Pressures

Abstract

 

Purpose

 

Deformation of the lamina cribrosa (LC) is thought to play a key role in the pathogenesis of glaucoma. Recent evidence implicates both intraocular pressure (IOP) and cerebrospinal fluid pressure (CSFP) in LC deformation. Therefore, we investigated the effects of acute in-vivo alterations in IOP and CSFP on 3D LC microstructure deformation.

 

Methods

 

In 3 macaque monkeys, we cannulated the anterior chamber of the eye and the lateral ventricle of the brain to control IOP and CSFP, respectively (Fig. 1A). OCT optic nerve head (ONH) imaging was performed under all combinations of IOPs (5, 15, 30 and 50mmHg) and CSFPs (5, 10, 25 and 40mmHg) conditions (Fig. 1B). For each eye, all scans were registered, and the same 3D LC region was analyzed for the following microstructure parameters: beam thickness, pore diameter and beam-pore ratio (ratio of beam thickness to pore diameter). A linear mixed effect model was used to determine the effect of translaminar pressure difference (TLPD = IOP - CSFP) and image quality (subjectively graded from 1 - 5) on LC microstructure.

 

Results

 

LC microstructure deformation varied substantially between scans under the different pressure conditions (Fig. 1C). Accounting for the effect of image quality, all LC microstructure parameters were statistically significantly associated with TLPD: for every 10mmHg increase in TLPD, beam thickness decreased (-0.33±0.16μm, p<0.05), pore diameter increased (0.18±0.09μm, p<0.05), and beam-pore ratio decreased (-0.020±0.007, p<0.01).

 

Conclusions

 

TLPD is significantly associated with LC microstructural deformation that occurs during acute pressure modulation. These in-vivo findings emphasize the importance of considering both IOP and CSFP when evaluating the role of the LC in glaucoma pathogenesis.  

 

(A, B) Diagram of the experimental design. (C) C-mode (top row) of LC microstructure from the same eye at 15mmHg (left column) and 50mmHg (right column), with automated segmentation labeling beams in green and pores in red (bottom row). Pore deformation is visible at elevated IOP in the enlarged image (middle row) and with segmentation (bottom row). (D) Scatter plot showing the association between LC microstructure parameters and TLPD in each monkey eye.