Relationship of optic nerve head blood flow and pulsatility to IOP and early-stage glaucomatous damage.

Abstract

Purpose : Previous studies using laser speckle flowgraphy (LSFG) have found that blood flow within the optic nerve head (ONH) is higher than normal during early stages of glaucomatous pathophysiology [PMID: 23737471, 31323681]. Here we sought to evaluate two LSFG parameters of pulsatility to determine whether they are similarly altered in early-stage non-human primate (NHP) experimental glaucoma (EG).

Methods : ONH tissue (capillary) blood flow was measured as the mean blur rate (MBR) parameter from the average of 3 sequential LSFG scans (Softcare Co., Ltd.) in each eye at each longitudinal time point, including two or more pre-glaucoma baseline sessions. Pulsatility was measured using two LSFG parameters: Beat Strength (BS), and BS normalized to MBR (BoM). Data were available for N=17 adult rhesus monkeys with unilateral EG (15F/2M, ages 5-17y). Stage of EG was monitored by OCT (Spectralis, Heidelberg Engineering GmbH) retinal nerve fiber layer thickness (RNFLT). Paired t-tests were used to compare parameters in EG eyes to their pre-glaucoma baseline and to their fellow control (FC) eyes at the onset of RNFLT loss. Linear regression was used to evaluate relationships between LSFG parameters and RNFLT or IOP.

Results : Fig1 shows that at onset of RNFLT loss (early stage) in EG eyes compared to baseline average, IOP was elevated from 12.9 ± 2.6 to 26.7 ± 11.9 mmHg, RNFLT was decreased from 97.4 ± 7.5 to 88.2 ± 7.1 µm and ONH minimum rim width (MRW) was decreased from 282.1 ± 34.3 to 200.7 ± 51.2 µm (each p<0.0001). LSFG MBR was elevated from 10.9 ± 2.2 to 11.7 ± 1.6 a.u. (which was significantly different from the change in FC eyes, p<0.01, but not compared to pre-EG baseline). LSFG BS was increased from 5.0 ± 1.5 to 6.5 ± 1.9 a.u. (p<0.01) and BoM was increased from 0.5 ± 0.1 to 0.6 ± 0.1 a.u. (p<0.05). Fig2 shows that MBR is already declining significantly with early-stage loss of RNFLT (p=0.02), while elevation of BS and BoM persist through this early stage, because of a strong influence of sustained IOP elevation.

Conclusions : These results confirm that ONH tissue (capillary) blood flow is elevated during early stages of glaucomatous damage, despite an apparent increase in vascular resistance within the ONH tissue (BoM), with increased beat strength driven by increased IOP.

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