Optic nerve head (ONH) hypercompliance and blood flow autoregulation dysfunction detected by OCT-angiography (OCTA) in early-stage experimental glaucoma (EG)

Abstract

Purpose : To probe ONH mechanical and vascular responses using OCTA in conjunction with manometrically controlled steps of intraocular pressure (IOP) elevation at an early stage of nonhuman primate (NHP) EG.

Methods : Data from 8 eyes of 4 NHP were available for this study. OCTA scans (Spectralis) consisting of 768x768 A-lines over 15x15° with an ART setting of 6 sweeps per B-scan were recorded bilaterally at baseline (in healthy control eyes, C) and longitudinally after induction of unilateral EG in 15 min intervals with IOP set to 10, 20, 30, 40, 50 and 60 mmHg, followed by a recovery step at 10 mmHg. Analysis was performed on the baseline scan series and at the onset of EG ONH rim thinning detected using the parameter minimum rim width (MRW; first MRW significantly below baseline; N=2/4 NHPs having EG onset at the time of this writing). Raw OCT/OCTA data were exported to custom software for segmentation and 3D measurements. From each structural OCT scan, we calculated ONH total rim volume (TRV) bounded laterally by the Bruch’s membrane opening (BMO), posteriorly by the BMO plane and anteriorly by the internal limiting membrane segmentation. ONH total rim vascular volume (TRVV) was calculated from the corresponding OCTA data and same boundaries. Volumetric vascular density was defined as TRVV/TRV. Peripapillary RNFL was evaluated using the volume outside BMO. Two-way ANOVA was applied to test effects of EG, acute IOP and their interaction.

Results : At onset of ONH rim thinning (MRW onset) in EG eyes, TRV was reduced as expected (p<0.0001, Fig1A), but also showed greater sensitivty to acute IOP elevation and recovery (p=0.06, Fig1B) than C. TRVV was also reduced at MRW onset in EG (p<0.0001) and exhibited greater sensitivity than C to acute IOP elevation and recovery (p=0.04, Fig2A). In C eyes, as IOP increased acutely, TRVV decreased less than TRV, such that ONH rim vascular density actually increased slightly for IOP >10 mmHg (Fig2B). However, in EG eyes, TRVV decreased more than TRV resulting in reduced vascular density for IOP >40 mmHg (Fig2B, p=0.04). Peripapillary RNFL thickness and vascular density were not affected by acute IOP elevation in C or EG (not shown).

Conclusions : These preliminary data suggest that ONH tissue hypercompliance and vascular autoregulation dysfunction can be detected using OCTA at the onset of rim thinning in EG.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.