Functional microvascular volume as a proportion of tissue volume is reduced in the RNFL but not the ONH rim at the onset of experimental glaucoma

Abstract

Purpose : To determine the extent of vascular changes at the onset of optic nerve head (ONH) rim and retinal nerve fiber layer (RNFL) tissue thinning.

Methods : Rhesus macaques (N=24, 17F/7M, ages 3-22 y) were imaged ~weekly by OCT and OCT-angiography (OCTA, Spectralis, 768x768x496 voxels over 15x15° centered on the ONH) during baseline and after induction of unilateral experimental glaucoma (EG, PMID: 27564522). OCT/A volumes were exported to custom software for segmentation and 3D measurements. From each structural OCT grid scan we calculated ONH rim volume (RV) bounded laterally by the Bruch’s membrane opening (BMO), posteriorly by the BMO plane and anteriorly by the internal limiting membrane (ILM) segmentations and RNFL volume outside BMO. Vascular volumes were calculated as the same set of voxels weighted by their OCTA signal and separated into large vessel (LV) and microvascular (MV) portions (Fig. 1). Repeated measures mixed effects models and post-hoc t-tests were applied to assess quantitative differences between baseline average values and those at the onset of significant change of ONH minimum rim width (MRW), RNFL thickness (RNFLT), and at the final time point.

Results : The duration from initiation of EG induction to MRW onset was an average (±SD) of 88±54d (N=23), to RNFLT onset was 109±69d (N=18), and to the final time point was 177±83d (N=24). There were no significant differences from baseline average values for any parameter in the group of fellow control eyes (Fig. 2). In EG eyes, as expected, there was a significant progressive decline of ONH rim volume and RNFL volume from baseline (Fig. 2A,B, p<0.0001). The proportion of tissue volume comprised by microvasculature declined significantly in the RNFL (Fig. 2D, p=0.003) such that it was 2.8±2.8% lower than baseline at onset of RNFLT thinning (p=0.0005), but did not change for the ONH rim (Fig. 2C, p=0.43). There was no change in the proportion of either the ONH rim volume or the RNFL volume comprised by large vessels (Fig. 2E,F, respectively, p=0.64, 0.09), nor in the two-dimensional area of large vessels as a proportion of either the ONH (BMO area) or RNFL area (Fig. 2G,H, respectively, p=0.69, 0.62) at any time point.

Conclusions : Functional microvascular volume as a proportion of tissue volume is reduced in the RNFL but not the ONH rim during early stages of EG in nonhuman primates.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.