Chieh‐Li Chen

, identifying abnormal vascular networks or vessel impairment zones in retinal and skin pathologies, detecting vessel patterns and angiogenesis in eyes with age-related macular degeneration and in skin and brain with tumors, and monitoring responses to hypoxia in the brain tissue. The purpose of this paper is to provide a technical oriented overview of the OCTA developments and their potential pre-clinical and clinical applications, and to shed some lights on its future perspectives. Because of its clinical translation to ophthalmology, this review intentionally places a slightly more weight on ophthalmic OCT angiography.

PURPOSE: To investigate optic disc perfusion differences in normal, primary open-angle glaucoma (POAG), and normal tension glaucoma (NTG) eyes using optical microangiography (OMAG) based optical coherence tomography (OCT) angiography technique. DESIGN: Cross-sectional, observational study. SUBJECTS: Twenty-eight normal, 30 POAG, and 31 NTG subjects. METHODS: One eye from each subject was scanned with a 68 kHz Cirrus HD-OCT 5,000-based OMAG prototype system centered at the optic nerve head (ONH) (Carl Zeiss Meditec Inc, Dublin, CA). Microvascular images were generated from the OMAG dataset by detecting the differences in OCT signal between consecutive B-scans. The pre-laminar layer (preLC) was isolated by a semi-automatic segmentation program. MAIN OUTCOME MEASURES: Optic disc perfusion, quantified as flux, vessel area density, and normalized flux (flux normalized by the vessel area) within the ONH. RESULTS: Glaucomatous eyes had significantly lower optic disc perfusion in preLC in all three perfusion metrics (p<0.0001) compared to normal eyes. The visual field (VF) mean deviation (MD) and pattern standard deviation (PSD) were similar between the POAG and NTG groups, and no differences in optic disc perfusion were observed between POAG and NTG. Univariate analysis revealed significant correlation between optic disc perfusion and VF MD, VF PSD, and rim area in both POAG and NTG groups (p≤0.0288). However, normalized optic disc perfusion was correlated with some structural measures (retinal nerve fiber layer thickness and ONH cup/disc ratio) only in POAG eyes. CONCLUSIONS: Optic disc perfusion detected with OMAG was significantly reduced in POAG and NTG groups compared to normal controls, but no difference was seen between POAG and NTG groups with similar levels of VF damage. Disc perfusion was significantly correlated with VF MD, VF PSD, and rim area in glaucomatous eyes. Vascular changes at the optic disc as measured using OMAG may provide useful information for diagnosis and monitoring of glaucoma.

Importance: Understanding the differences in vascular microcirculation of the peripapillary retinal nerve fiber layer (RNFL) between the hemispheres in eyes with glaucoma with single-hemifield visual field (VF) defects may provide insight into the pathophysiology of glaucoma. Objective: To investigate the changes in the microcirculation of the peripapillary RNFL of eyes with glaucoma by using optical microangiography. Design, Setting, and Participants: Eyes with glaucoma and single-hemifield VF defect and normal eyes underwent scanning using an optical microangiography system covering a 6.7 × 6.7-mm2 area centered at the optic nerve head. The RNFL microcirculation was measured within an annulus region centered at the optic nerve head divided into superior and inferior hemispheres. Blood flux index (the mean flow signal intensity in the vessels) and vessel area density (the percentage of the detected vessels in the annulus) were measured. Main Outcomes and Measures: Differences in microcirculation between the hemispheres in eyes with glaucoma and normal eyes and correlations among blood flow metrics, VF thresholds, and clinical optical coherence tomography structural measurements were assessed. Results: Twenty-one eyes from 21 patients with glaucoma (7 men and 14 women; mean [SD] age, 63.7 [9.9] years) and 20 eyes from 20 healthy control individuals (9 men and 11 women; mean [SD] age, 68.3 [10.7] years) were studied. In eyes with glaucoma, the abnormal hemisphere showed a thinner RNFL (mean [SE] difference, 23.5 [4.5] μm; 95% CI, 15.1-32.0 µm; P < .001), lower RNFL blood flux index (mean [SE] difference, 0.04 [0.01]; 95% CI, 0.02-0.05; P < .001), and less vessel area density (mean [SE] difference, 0.08% [0.02%]; 95% CI, 0.05%-0.10%; P < .001) than did the normal hemisphere. Compared with normal eyes, reduced RNFL microcirculation was found in the normal hemisphere of eyes with glaucoma, measured by mean [SE] differences in blood flux index (0.06 [0.01]; 95% CI, 0.04-0.09; P < .001) and vessel area density (0.04% [0.02%]; 95% CI, 0.02%-0.08%; P = .003) but not in RNFL thickness (3.4 [4.7] μm; 95% CI, -6.2 to 12.9 µm; P = .48). Strong correlations were found between the blood flux index and VF mean deviation (Spearman ρ = 0.44; P = .045) and RNFL thickness (Spearman ρ = 0.65; P = .001) in the normal hemisphere of the eye with glaucoma. Conclusions and Relevance: Reduced RNFL microcirculation was detected in the normal hemisphere of eyes with glaucoma, with strong correspondence with VF loss and RNFL thinning. Although the results suggest that vascular dysfunction precedes structural changes seen in glaucoma, longitudinal studies would be needed to confirm this finding.

BACKGROUND: To investigate the differences of perfusion in the optic nerve head (ONH) between normal and glaucomatous eyes using optical microangiography (OMAG) based optical coherence tomography (OCT) angiography technique. METHODS: One eye from each subject was scanned with a 68 kHz Cirrus 5000 HD-OCT-based OMAG prototype system centered at the ONH (Carl Zeiss Meditec Inc, Dublin, CA, USA). Microvascular images were generated from the OMAG dataset by detecting the differences in OCT signal between consecutive B-scans. The pre-laminar layer (preLC) was isolated by a semi-automatic segmentation program. En face OMAG images for preLC were generated using signals with highest blood flow signal intensity. ONH perfusion was quantified as flux, vessel area density, and normalized flux within the ONH. Standard t-tests were performed to analyze the ONH perfusion differences between normal and glaucomatous eyes. Linear regression models were constructed to analyze the correlation between ONH perfusion and other clinical measurements. RESULTS: Twenty normal and 21 glaucoma subjects were enrolled. Glaucomatous eyes had significantly lower ONH perfusion in preLC in all three perfusion metrics compared to normal eyes (P≤0.0003). Significant correlations between ONH perfusion and disease severity as well as structural changes were detected in glaucomatous eyes (P≤0.012). CONCLUSIONS: ONH perfusion detected by OMAG showed significant differences between glaucoma and normal controls and was significantly correlated with disease severity and structural defects in glaucomatous eyes. ONH perfusion measurement using OMAG may provide useful information for detection and monitoring of glaucoma.