During progression of glaucomatous damage, the rate of functional microvascular tissue loss exceeds loss of non-vascular tissue within the retinal nerve fiber layer, but declines proportionally within the optic nerve head neuroretinal rim

Abstract

Purpose : To compare the rate of progression of vascular changes to that of other parameters of structural damage in nonhuman primate (NHP) experimental glaucoma (EG).

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 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 (Figs. 1,2). Linear regression was used to compare rates of change between EG and fellow control (FC) eyes for each parameter after normalization to their pre-EG baseline average values.

Results : The duration of longitudinal follow-up after initiation of EG induction ranged from 54 to 407 days (median: 180, IQR: 105-228 days). There was no significant change over time for BMO area (Table in Fig. 2), thus, changes in rim volume reflect posterior deformation, axon loss and compression. ONH rim volume declined significantly in EG but not control eyes. RNFL volume and average thickness declined more rapidly in EG than control eyes. The proportion of RNFL tissue comprised by microvasculature declined significantly in EG eyes, but increased slightly in control eyes. This pattern was also found for the RNFL microvasculature when expressed as a proportion of non-vascular RNFL tissue volume. Within the ONH rim, neither large vessels, nor microvascular proportion changed significantly in EG or control eyes. The large vessel proportion of RNFL tissue increased slightly in EG but did not change in control eyes.

Conclusions : The rate of loss of functional microvascular tissue exceeds that of the non-vascular portion of the RNFL during progression of NHP EG. In contrast, the proportion of ONH rim tissue comprised of large and small vessels remains constant as the rim becomes thinner.

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