A novel method to determine axon-level IOP-induced insult

Abstract

Purpose : To introduce an axon-centric approach to determine IOP-induced neural tissue insult in the optic nerve head (ONH).

Methods : Optical coherence tomography (OCT) images of a normal monkey ONH were acquired at IOPs of 10 and 40mmHg (Figure 1). IOP-induced ONH deformations were tracked using digital volume correlation (DVC). The non-collagenous ONH volume incorporating lamina cribrosa (LC) beam and pore details was formed by combining manual reconstructions from OCT images and polarized light microscopy of cryosections. The large blood vessels were later removed from the non-collagenous ONH volume. Axon paths from the retinal nerve fiber layer to the optic nerve were approximated by a custom fluid tracing technique. Experimental deformations were combined with local axon paths to determine the IOP-induced stretch along the axons (longitudinal) and the compression perpendicular to the axons (transverse). The largest longitudinal stretch and transverse compression over the whole axon were assigned as the “worst-case” insults for the axon. For analysis, the axons were grouped into six regions.

Results : The largest longitudinal stretch insult in the temporal region (range 5% to 21%) was 2.5x that in the superior (ST, SN) and nasal (IN, N) regions. The peak value of transverse compression insult in the inferior nasal region (7%) was 16% higher compared to all other regions.

Conclusions : Longitudinal stretch and transverse compression represent distinct mechanisms of potential axon damage. The presented approach has the potential to help identify the link between IOP-induced deformation and neural tissue damage and glaucoma.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

 

Analysis methodology. A) OCT imaging of the monkey eye. B) Raster B-scans at baseline IOP of 10 mmHg and elevated IOP of 40 mmHg. C) Experimental ONH deformation obtained using DVC. D) Non-collagenous ONH volume without large blood vessels reconstructed from OCT and microscopy. E) Axons in anterior and posterior views. The axons are colored according to six regions. Note complex LC effects discernible in the posterior view. F) Close-up of cup region showing axons crossing between regions

 

IOP-induced maximum stretch along the axon (left column) and compression transverse to the axon (right column). The top row shows box plots of the distribution of the two types of insult for the six regions. The bottom row shows axons colored according to the “worst-case” or maximum insult along the axon path in anterior and posterior views