Increased Optic Nerve Head Capillary Blood Flow in Early Primary Open-Angle Glaucoma

Abstract

PURPOSE. Blood flow in the optic nerve head (ONH) is known to be reduced in eyes with advanced glaucoma. However, experimental results from non-human primates suggest an initial increase in ONH blood flow at the earliest stages of damage. This study assesses flow and pulsatile hemodynamics across a range of severities to test the hypothesis that this also occurs in human glaucoma. METHODS. Laser speckle flowgraphy was used to measure average mean blur rate (MBR ave) within ONH tissue (a correlate of capillary blood flow) and the pulsatile waveform in 93 eyes with functional loss and 74 glaucoma suspect/fellow eyes without functional loss. These were compared against results from 92 healthy control eyes. Parameters produced by the instrument's software were age-corrected, then compared between groups using generalized estimating equation models. RESULTS. The mean MBR ave in the control eyes was 12.5 units. In glaucoma suspect/fellow eyes, the mean was 16.4 units, higher with P < 0.0001. In eyes with functional loss, the mean was 13.8 units, lower than eyes without functional loss with P < 0.0001, although still higher than control eyes with P ¼ 0.0096. Analysis of the pulsatile waveform suggested that the deceleration in flow as it approaches its maximum across the cardiac cycle was delayed in glaucoma. CONCLUSIONS. Blood flow within ONH capillaries was higher in glaucoma suspect eyes than in healthy controls. It was less elevated in eyes that had developed functional loss. The mechanisms causing these changes and their relation to concurrent changes in pulsatile hemodynamics remain under investigation.

Characterization of laser speckle flowgraphy pulse waveform parameters for the evaluation of the optic nerve head and retinal circulation

“…It is well known that a greater β-PPA area is a risk for progression of glaucoma 37 , 38 , being associated with the extent of glaucomatous visual field damage 39 – 41 . Therefore, lower MT-Skew associated with a greater β-PPA area seems compatible with an increase in glaucomatous damage or risk for glaucoma, and also with the previous results of lower MT-Skew reported in NTG 24 and POAG 26 . It is possible that after adjustment for age, DBP, and HR, MT-Skew could reflect circulatory changes in the ONH tissue associated with the β-PPA area.…”

“…Regarding the correlation to ocular factors, we found that the MT-Skew was significantly negatively correlated with the β-PPA area (Table 4 ). In previous reports, MT-Skew was significantly lower in patients with normal-tension glaucoma (NTG) 24 and primary open-angle glaucoma (POAG) 26 than in those with normal eyes. It is well known that a greater β-PPA area is a risk for progression of glaucoma 37 , 38 , being associated with the extent of glaucomatous visual field damage 39 – 41 .…”

“…Since many studies have shown that a narrower CRAE is associated with aging and cardiovascular diseases 42 and also with glaucoma and its development 43 – 46 , the current finding implied that a higher MT-BOS may be suggestive of compromised retinal circulation. Gardiner et al 26 reported that a lower MT-BOS in glaucoma suspect/fellow eyes without a functional loss than in normal eyes was associated with a higher MT or higher blood flow in these eyes than in normal eyes. Conversely, Takeshima et al 27 reported that MT-BOS increased significantly after trabeculectomy, which could suggest an increased ONH circulation resulting from the ONH vascular bed reaction (in which the autoregulation mechanism was compromised 47 , 48 ) to increased perfusion pressure due to IOP reduction.…”

“…Conversely, LSFG pulse waveforms themselves are relatively free from such effects; therefore, they could be more suited for inter-individual comparison of the ONH or retinal circulatory status than the MT or MV. Several LSFG pulse waveform parameters reportedly showed significant differences between normal and glaucoma eyes 24 – 26 , between various disease stages of glaucoma 24 , and a significant change after trabeculectomy 27 , 28 , and water drinking 29 . Further, a significant correlation of leukocyte glutathione levels, an indicator of mitochondrial dysfunction, was found with one LSFG pulse waveform parameter for MT in glaucoma patients 30 .…”

“…While several studies have looked at the differences of LSFG pulse waveform parameters between the glaucoma and normal eyes 24 – 26 or between sexes 6 , 7 , 17 , it is still largely unclear which LSFG pulse waveform parameters reflect the pathophysiology of ocular fundus circulation more effectively. We assumed that there should be particularly useful waveform parameters for ocular circulation studies.…”