The impact of ocular blood flow in glaucoma.

Optical Coherence Tomography Angiography of Optic Disc Perfusion in Glaucoma

Purpose To compare optic disc perfusion between normal subjects and subjects with glaucoma using optical coherence tomography (OCT) angiography and to detect optic disc perfusion changes in glaucoma. Design Observational, cross-sectional study. Participants Twenty-four normal subjects and 11 patients with glaucoma were included. Methods One eye of each subject was scanned by a high-speed 1050-nm–wavelength swept-source OCT instrument. The split-spectrum amplitude-decorrelation angiography (SSADA) algorithm was used to compute 3-dimensional optic disc angiography. A disc flow index was computed from 4 registered scans. Confocal scanning laser ophthalmoscopy (cSLO) was used to measure disc rim area, and stereo photography was used to evaluate cup/disc (C/D) ratios. Wide-field OCT scans over the discs were used to measure retinal nerve fiber layer (NFL) thickness. Main Outcome Measures Variability was assessed by coefficient of variation (CV). Diagnostic accuracy was assessed by sensitivity and specificity. Comparisons between glaucoma and normal groups were analyzed by Wilcoxon rank-sum test. Correlations among disc flow index, structural assessments, and visual field (VF) parameters were assessed by linear regression. Results In normal discs, a dense microvascular network was visible on OCT angiography. This network was visibly attenuated in subjects with glaucoma. The intra-visit repeatability, inter-visit reproducibility, and normal population variability of the optic disc flow index were 1.2%, 4.2%, and 5.0% CV, respectively. The disc flow index was reduced by 25% in the glaucoma group ( P = 0.003). Sensitivity and specificity were both 100% using an optimized cutoff. The flow index was highly correlated with VF pattern standard deviation ( R 2  = 0.752, P = 0.001). These correlations were significant even after accounting for age, C/D area ratio, NFL, and rim area. Conclusions Optical coherence tomography angiography, generated by the new SSADA, repeatably measures optic disc perfusion and may be useful in the evaluation of glaucoma and glaucoma progression.

Importance Vascular factors may have important roles in the pathophysiology of glaucoma. A practical method for the clinical evaluation of ocular perfusion is needed to improve glaucoma management. Objective To detect peripapillary retinal perfusion in glaucomatous eyes compared with normal eyes using optical coherence tomography (OCT) angiography. Design, Setting, and Participants Prospective observational study performed from July 24, 2013, to April 17, 2014. Participants were recruited and tested at Casey Eye Institute, Oregon Health & Science University. In total, 12 glaucomatous eyes and 12 age-matched normal eyes were analyzed. The optic disc region was imaged twice using a 3 × 3-mm scan by a 70-kHz, 840-nm-wavelength spectral OCT system. The split-spectrum amplitude-decorrelation angiography algorithm was used. Peripapillary flow index was calculated as the mean decorrelation value in the peripapillary region, defined as a 700-µm-wide elliptical annulus around the disc. Peripapillary vessel density was the percentage area occupied by vessels. The data statistical analysis was performed from October 30, 2013, to May 30, 2014. Main Outcomes and Measures Variability was assessed by the coefficient of variation. The Mann-Whitney test was used to compare the 2 groups of eyes. Correlations between vascular and visual field variables were assessed by linear regression analysis. Results In 12 normal eyes, a dense microvascular network around the disc was visible on OCT angiography. In 12 glaucomatous eyes, this network was visibly attenuated globally and focally. In normal eyes, between-visit reproducibilities of peripapillary flow index and peripapillary vessel density were 4.3% and 2.7% of the coefficient of variation, respectively, while the population variabilities of peripapillary flow index and peripapillary vessel density were 8.2% and 3.0% of the coefficient of variation, respectively. Peripapillary flow index and peripapillary vessel density in glaucomatous eyes were lower than those in normal eyes ( P r  = −0.808) and peripapillary vessel density (Pearson r  = −0.835) were highly correlated with visual field pattern standard deviation in glaucomatous eyes ( P  = .001 for both). The areas under the receiver operating characteristic curve for normal vs glaucomatous eyes were 0.892 for peripapillary flow index and 0.938 for peripapillary vessel density. Conclusions and Relevance Using OCT angiography, reduced peripapillary retinal perfusion in glaucomatous eyes can be visualized as focal defects and quantified as peripapillary flow index and peripapillary vessel density, with high repeatability and reproducibility. Quantitative OCT angiography may have value in future studies to determine its potential usefulness in glaucoma evaluation.

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Optical coherence tomography angiography of the peripapillary retina in glaucoma

Optic nerve head (ONH) blood flow may be associated with glaucoma development. A reliable method to quantify ONH blood flow could provide insight into the vascular component of glaucoma pathophysiology. Using ultrahigh-speed optical coherence tomography (OCT), we developed a new 3D angiography algorithm called split-spectrum amplitude-decorrelation angiography (SSADA) for imaging ONH microcirculation. In this study, a method to quantify SSADA results was developed and used to detect ONH perfusion changes in early glaucoma. En face maximum projection was used to obtain 2D disc angiograms, from which the average decorrelation values (flow index) and the percentage area occupied by vessels (vessel density) were computed from the optic disc and a selected region within it. Preperimetric glaucoma patients had significant reductions of ONH perfusion compared to normals. This pilot study indicates OCT angiography can detect the abnormalities of ONH perfusion and has the potential to reveal the ONH blood flow mechanism related to glaucoma.

Quantitative OCT angiography of optic nerve head blood flow

Optic disc blood flow velocity was measured in healthy patients, those with primary open angle glaucoma (POAG), and patients with normal pressure glaucoma (NPG). The velocity of the red blood cells (RBCs) in the capillaries of the optic nerve head (ONH) has been measured with a laser Doppler velocimeter (LDV), and blood viscosity has been evaluated notably by determining the aggregability of the RBCs with an erythroaggregameter. Our results in POAG patients and NPG patients showed that their optic nerve blood flow velocity was reduced and that the aggregability of the RBCs was increased. The hyperaggregability of the erythrocytes is responsible for the increase of the local viscosity in the papillary capillary network. These haemodynamic modifications observed in patients with glaucoma support the hypothesis of a vasogenic mechanism that could impair the optic nerve in glaucoma patients.

https://bjo.bmj.com/content/bjophthalmol/78/6/449.full.pdf

Optic nerve head blood flow using a laser Doppler velocimeter and haemorheology in primary open angle glaucoma and normal pressure glaucoma.

Blood flow rate in the microvasculature of the optic nerve head in primary open angle glaucoma. A new approach.

The vascular participation to the optic nerve pathogenesis has been contradicted. The red blood cell velocity in the optic nerve capillary with a laser Doppler velocimeter, an atraumatic and reliable method, and the aggregability was determined with an erythroaggregameter to know whether an erythrocyte hyperaggregability could slow down the optic nerve blood flow as it has been previously demonstrated in an experimental study. The experiment on the open angle glaucoma patients showed that their optic nerve blood flow was reduced, and their erythrocyte aggregability significantly increased. The two parameters were not significantly correlated, certainly because of a local papillary autoregulation and of the papilla vessels variability, those two factors could modulate the blood flow response to blood qualitative changes. The erythrocyte hyperaggregability could be explained by erythrocyte membrane modifications that could agree with the glaucoma heredity.

[Hemo-rheology of glaucomatous neuropathy].

We study capillary microcirculation on the optic nerve head and its interrelation with blood rheological modifications. The mean maximal velocity has been evaluated in the capillaries of the rabbit optic nerve with a laser doppler velocimeter, in physiological conditions and after intravenous Dextrane 250 injections. Dextrane 250 increases red blood cells aggregation and induces blood hyperviscosity at low flow rates. This hyperaggregation is determined with a reflectometric method. Experimental results show a significant reduction of blood velocity when blood viscosity increases. In our present study, we compare blood capillaries flow rate in the optic nerve, between two groups: healthy humans and subjects suffering from glaucoma. The aggregation level is simultaneously measured for the two groups. First results seem to prove that blood flow rate decrease is associated with red blood cells aggregation increase for the second group.

H. Hamard

Papers

Optic nerve head blood flow using a laser Doppler velocimeter and haemorheology in primary open angle glaucoma and normal pressure glaucoma.

Blood flow rate in the microvasculature of the optic nerve head in primary open angle glaucoma. A new approach.

[Hemo-rheology of glaucomatous neuropathy].

[Laser-Doppler velocimetry on the optic nerve head and hemorheology. Animal experiments. First results in humans].

Vélocimétrie laser-Doppler sur la tête du nerf optique et hémorhéologie. Expérimentation animale. Premiers résultats chez l'homme.