Systemic Determinants of Peripapillary Vessel Density in Healthy African Americans: The African American Eye Disease Study.

PURPOSE: To determine the relationship between systemic factors and radial peripapillary capillary (RPC) vessel density (VD) in healthy African American (AA) participants of the African American Eye Disease Study. DESIGN: A population-based, cross-sectional study. METHODS: A total of 4135 eyes from 2127 AA participants aged 40 years and older in Inglewood, California, were imaged for 6×6-mm optic disc scans on a spectral-domain optical coherence tomography angiography (OCTA) device. Of these, 1029 eyes from 1029 participants who met the inclusion and exclusion criteria were analyzed, including only 1 eye per participant. Custom software was used to quantify RPC VD. Multivariate linear regression was used to identify systemic factors associated with RPC VD with a significance level set at 0.05. The contribution of each variable to the final model was estimated with the magnitude of standardized regression coefficients (SRCs). The fit of the final model was measured by R2. RESULTS: The average RPC VD was 0.346±0.045. Controlling for signal strength, the systemic variables in the final multivariate model associated with reduced RPC VD were older age (ß = -0.0123 per decade; SRC = -0.2733; P < .0001), male sex (ß = -0.0067; SRC = -0.0716; P = .0060), and longer diabetes duration (ß = -0.0022 per 5 years; SRC = -0.0527; P = .0427). The model R2 was 0.3689. CONCLUSIONS: Age, sex, and systemic influences, such as diabetes duration, need to be considered when assessing changes in RPC VD in glaucoma and other ocular diseases. Longitudinal studies are needed to investigate whether reduced RPC VD and the factors that affect it are associated with an increased risk of developing glaucomatous nerve damage.

Effect of Scan Size on Glaucoma Diagnostic Performance Using OCT Angiography En Face Images of the Radial Peripapillary Capillaries.

PRECIS: When comparing 4.5×4.5 mm to 6.0×6.0 mm optical coherence tomography angiography scans of the radial peripapillary capillaries (RPCs) for glaucoma diagnostic capability, there was a trend of 4.5 scans outperforming 6.0 scans, especially for inferior, nasal, and superior quadrants. OBJECTIVES: The main purpose of this study was to compare diagnostic ability of peripapillary vessel parameters from 4.5×4.5 mm (4.5) and 6.0×6.0 mm (6.0) spectral-domain optical coherence tomography angiography scans of the RPC in detecting primary open-angle glaucoma from nonglaucoma eyes. METHODS: Consecutive patients from an academic glaucoma clinic underwent 4.5 and 6.0 scans (CIRRUS HD-OCT 5000 with AngioPlex OCT Angiography; ZEISS, Dublin, CA). Automatic segmentation created en face RPC images. Vessel area density, vessel skeleton density, and flux were calculated using custom quantification software, and perfusion density and flux index (FI) using automated quantification software. Area under the curve statistics included age and hypertension in the analysis. RESULTS: Of 173 eyes from 123 patients who underwent both 4.5 and 6.0 imaging, 32 primary open-angle glaucoma eyes from 32 patients and 95 nonglaucoma eyes from 95 patients were studied. For the global region of 4.5 versus 6.0 scans, area under the curve was 0.940 and 0.916 for vessel area density (P=0.286); 0.941 and 0.921 for vessel skeleton density (P=0.385); 0.942 and 0.916 for flux (P=0.239); 0.912 and 0.884 for perfusion density (P=0.103); and 0.913 and 0.865 for FI (P=0.159), respectively. For the quadrant regions, 4.5 images significantly outperformed 6.0 images for the superior and inferior quadrants for flux and superior and nasal quadrants for FI (P-values=0.007, 0.047, 0.011, 0.007, respectively); other quadrant differences were not significant. CONCLUSIONS: Parameters from 4.5 scans generally outperformed those from 6.0 scans in the global and quadrant regions, suggesting greater digital resolution in 4.5 scans of the immediate peripapillary RPC is important in detecting glaucomatous changes.

Machine Learning Models for Diagnosing Glaucoma from Retinal Nerve Fiber Layer Thickness Maps.

PURPOSE: To assess the diagnostic accuracy of multiple machine learning models using full retinal nerve fiber layer (RNFL) thickness maps in detecting glaucoma. DESIGN: Case-control study. PARTICIPANTS: A total of 93 eyes from 69 patients with glaucoma and 128 eyes from 128 age- and sex-matched healthy controls from the Los Angeles Latino Eye Study (LALES), a large population-based, longitudinal cohort study consisting of Latino participants aged ≥40 years residing in El Puente, California. METHODS: The 6×6-mm RNFL thickness maps centered on the optic nerve head (Cirrus 4000; Zeiss, Dublin, CA) were supplied to 4 different machine learning algorithms. These models included 2 conventional machine learning algorithms, Support Vector Machine (SVM) and K-Nearest Neighbor (KNN), and 2 convolutional neural nets, ResNet-18 and GlaucomaNet, which was a custom-made deep learning network. All models were tested with 5-fold cross validation. MAIN OUTCOME MEASURES: Area under the curve (AUC) statistics to assess diagnostic accuracy of each model compared with conventional average circumpapillary RNFL thickness. RESULTS: All 4 models achieved similarly high diagnostic accuracies, with AUC values ranging from 0.91 to 0.92. These values were significantly higher than those for average circumpapillary RNFL thickness, which had an AUC of 0.76 in the same patient population. CONCLUSIONS: Superior diagnostic performance was achieved with both conventional machine learning and convolutional neural net models compared with circumpapillary RNFL thickness. This supports the importance of the spatial structure of RNFL thickness map data in diagnosing glaucoma and further efforts to optimize our use of this data.

Ocular Determinants of Peripapillary Vessel Density in Healthy African Americans: The African American Eye Disease Study.

Purpose: The African American (AA) population has unique ocular anatomic characteristics and a disproportionately high incidence of glaucoma, which is associated with lower peripapillary vessel density (VD). This study aimed to identify ocular determinants of peripapillary VD in healthy AAs. Methods: This was a cross-sectional, population-based study of 1029 AAs, ages 40 and older. Participants underwent examination to obtain axial length (AL), IOP, central corneal thickness (CCT), mean retinal nerve fiber layer (RNFL) thickness, visual field mean deviation (MD), and 6 × 6-mm optical coherence tomography angiography scans of the optic nerve. Participants with glaucoma, vision-threatening diabetic retinopathy, or other relevant ocular disease were excluded. Prototype software was used to quantify VD. A multivariable regression model, controlling for age and signal strength, identified the ocular variables that predicted peripapillary VD. The contribution of each variable was assessed with the magnitude of standardized regression coefficients (SRC). Results: Based on univariate regressions, AL, RNFL thickness, and MD had significant associations with peripapillary VD (all P < 0.001). In the final multivariate model, lower mean RNFL thickness (ß = 0.0022, P < 0.001, SRC = 0.542) and longer AL (ß = -0.0055, P < 0.001, SRC = -0.118) were associated with lower peripapillary VD, controlling for age and signal strength, with model R2 of 0.69. Conclusions: Thinner RNFL and longer AL were the most influential ocular determinants of lower peripapillary perfusion in healthy AA eyes. Additional research is needed to clarify whether longer AL increases risk of glaucoma by affecting capillary perfusion.

Diagnostic Performance of Macular Versus Peripapillary Vessel Parameters by Optical Coherence Tomography Angiography for Glaucoma.

PURPOSE: To compare the diagnostic ability of the vessel parameters in macular and peripapillary regions measured using spectral-domain optical coherence tomography angiography (SD-OCTA) in differentiating primary open-angle glaucoma (POAG) from healthy eyes. METHODS: POAG patients and healthy subjects underwent 6 × 6-mm scans centered on the macula and optic nerve head. Commercially available automatic segmentation created en face images from SD-OCTA of the superficial retinal layer (SRL) of the macular (m) and peripapillary (cp) regions. Vessel area density (VAD), vessel skeleton density (VSD), vessel complexity index (VCI), and flux were calculated. Area under curve (AUC) statistics controlled for age and intereye correlation. RESULTS: Of 126 eyes from 79 patients who underwent SD-OCTA macula and peripapillary imaging, 50 eyes from 35 POAG patients and 37 healthy eyes from 25 control subjects had good quality imaging and were studied. Diagnostic accuracies of four perfusion parameters, VAD, VSD, VCI, and flux, were significantly greater in the peripapillary compared with the macular regions. For VAD, the cpAUC was 0.84 and mAUC was 0.73 (AUC difference: P = 0.026). For VSD, the cpAUC was 0.84 and mAUC was 0.72 (ΔP = 0.015). For VCI, the cpAUC was 0.80 and mAUC was 0.70 (ΔP = 0.045). For flux, the cpAUC = 0.87 and mAUC was 0.76 (ΔP = 0.0091). CONCLUSIONS: Peripapillary perfusion parameters performed better than macular perfusion parameters for glaucoma diagnosis, supporting the idea that glaucomatous superficial retinal vascular changes are more pronounced in the peripapillary region. TRANSLATIONAL RELEVANCE: The diagnostic accuracy of OCTA perfusion parameters of the superficial retinal microcirculation was greater for the peripapillary region than the macular region in the diagnosis of glaucoma.

Peripapillary microvasculature in the retinal nerve fiber layer in glaucoma by optical coherence tomography angiography: focal structural and functional correlations and diagnostic performance.

PURPOSE: To quantify peripapillary microvasculature within the retinal nerve fiber layer (RNFL) in primary open-angle glaucoma (POAG) and normal eyes, determine association of perfusion parameters with structural and functional measures, and report diagnostic accuracy of perfusion parameters. PATIENTS AND METHODS: POAG and normal patients underwent 6×6 mm2 optic nerve head scans (Angioplex optical coherence tomography angiography [OCTA]; Cirrus HD-OCT 5000) and Humphrey Field Analyzer II-i 24-2 visual field (VF) testing. Prototype software performed semiautomatic segmentation to create RNFL en face images and quantified vessel area density (VAD), vessel skeleton density (VSD), and vessel complexity index (VCI) in the optic nerve head globally and focally. Generalized estimating equations models assessed association of OCTA parameters with VF mean deviation (MD) and RNFL thickness. RESULTS: Thirty-eight POAG and 17 normal eyes were studied. Global VAD, VSD, and VCI were reduced in mild POAG vs normal (P<0.02) and moderate-severe vs mild POAG (P<0.04). Stepwise focal reductions across disease stage were demonstrated for OCTA parameters in the inferior hemisphere (P<0.05); reduction in OCTA parameters in mild POAG vs normal was demonstrated in inferior and superior quadrants (P<0.05). Reduced global VF MD was associated with reduced VAD, VSD, and VCI (P=0.0007, 0.0013, <0.0001; R 2=0.449, 0.312, 0.399, respectively), and global RNFL thickness was associated with VAD, VSD, and VCI (P<0.0001; R 2=0.499, 0.524, 0.542), superior and inferior hemifield MD were associated with corresponding VAD, VSD, and VCI (P≤0.001; R 2 from 0.208 to 0.513). RNFL thickness in all quadrants was associated with corresponding OCTA parameters (P<0.05; R 2 from 0.213 to 0.394), except temporal VAD and VCI. Area under curves for VAD, VSD, and VCI demonstrated good diagnostic ability (0.868, 0.855, 0.868; P<0.0001). CONCLUSION: Glaucomatous eyes showed stepwise reductions in RNFL microcirculation across severity; focal reductions in the inferior hemisphere and inferior and superior quadrants were most significant. OCTA parameters had stronger associations with structural rather than functional measures of glaucoma.

Structural and Functional Associations of Macular Microcirculation in the Ganglion Cell-Inner Plexiform Layer in Glaucoma Using Optical Coherence Tomography Angiography.

PURPOSE: To quantify retinal microvasculature within the macular ganglion cell-inner plexiform layer (GCIPL) in primary open-angle glaucoma (POAG) and normal eyes, determine association of vessel parameters with structural and functional measures, and report diagnostic accuracy of vessel parameters. METHODS: POAG and normal patients underwent 6×6 mm macula scans [Angioplex optical coherence tomography angiography (OCTA); Cirrus HD-OCT 5000]; and Humphrey Field Analyzer II-i 24-2 visual field (VF). Prototype software performed semiautomatic segmentation to create GCIPL en face images, and quantified vessel area density (VAD), vessel skeleton density (VSD), and vessel complexity index (VCI) for the macula (globally, hemifields, and 6 focal sectors). Linear regression assessed association of OCTA parameters with VF mean deviation (MD) and GCIPL thickness globally and focally. RESULTS: A total of 34 POAG and 21 normal eyes were studied. VAD, VSD, and VCI were reduced in POAG versus normal (0.463 vs. 0.486, P=0.00029; 0.230 vs. 0.219, P=0.0014; 1.15 vs. 1.09, P=0.0044, respectively), with a trend of worsening with increased POAG severity. Reduced global VF MD was associated with reduced VAD and VCI, controlling for age and intereye correlation (P=0.0060, 0.0080; R=0.205, 0.211). Both superior and inferior hemifield MD were associated with corresponding VAD, VSD, and VCI (all P<0.007; R ranged from 0.12 to 0.29). Global GCIPL thickness was not associated with global OCTA parameters, and only inferior sector GCIPL thickness was associated with corresponding VAD, VSD, and VCI (P<0.05; R ranged from 0.15 to 0.16). Area under curves for VAD, VSD, and VCI were fair to good (0.83, 0.79, 0.82; respectively; P<0.0001). CONCLUSIONS: Glaucomatous eyes had reduced GCIPL microcirculation. OCTA parameters had stronger associations with functional rather than structural measures of glaucoma. This observation deserves further study.