ASSESSMENT OF RETINAL BLOOD FLOW IN DIABETIC RETINOPATHY USING DOPPLER FOURIER-DOMAIN OPTICAL COHERENCE TOMOGRAPHY.

PURPOSE: To evaluate retinal blood flow measurements in normal eyes and eyes with varying levels of diabetic retinopathy (DR) using Doppler Fourier-domain optical coherence tomography (FD-OCT). METHODS: Twenty-two eyes of 19 subjects, 10 with severe nonproliferative DR (NPDR) and 12 with proliferative DR (PDR), were compared with 44 eyes of 40 healthy control subjects. All eyes were scanned by RTvue FD-OCT. Color disk photographs and cube/volume scans of the optic nerve head were obtained. Doppler OCT scans and accessory imaging data were imported into Doppler OCT of Retinal Circulation grading software to calculate TRBF and vascular parameters (e.g., venous and arterial cross-sectional area). Measurements were compared between cases and controls using independent t-tests. RESULTS: Mean TRBF was 44.98 ± 9.80 (range: 30.18-64.58) µL/minute for normal eyes, 35.80 ± 10.48 (range: 20.69-49.56) µL/minute for eyes with severe NPDR, and 34.79 ± 10.61 (range: 16.77-48.9) µL/minute for eyes with PDR. Mean TRBF was significantly lower in eyes with severe NPDR (P = 0.01) and PDR (P = 0.003) than in normal eyes. CONCLUSION: Total retinal blood flow was significantly lower in eyes with severe NPDR and PDR compared with normal eyes. Retinal blood flow determined by Doppler OCT may be a useful parameter for evaluating patients with DR.

Postprocessing algorithms to minimize fixed-pattern artifact and reduce trigger jitter in swept source optical coherence tomography.

We propose methods to align interferograms affected by trigger jitter to a reference interferogram based on the information (amplitude/phase) at a fixed-pattern noise location to reduce residual fixed-pattern noise and improve the phase stability of swept source optical coherence tomography (SS-OCT) systems. One proposed method achieved this by introducing a wavenumber shift (k-shift) in the interferograms of interest and searching for the k-shift that minimized the fixed-pattern noise amplitude. The other method calculated the relative k-shift using the phase information at the residual fixed-pattern noise location. Repeating this wavenumber alignment procedure for all A-lines of interest produced fixed-pattern noise free and phase stable OCT images. A system incorporating these correction routines was used for human retina OCT and Doppler OCT imaging. The results from the two methods were compared, and it was found that the intensity-based method provided better results.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF TIME COURSE OF CHOROIDAL NEOVASCULARIZATION IN RESPONSE TO ANTI-ANGIOGENIC TREATMENT.

PURPOSE: To use optical coherence tomography (OCT) angiography to monitor the short-term blood flow changes in choroidal neovascularization (CNV) in response to treatment. METHODS: In this retrospective report, a case of exudative CNV was followed closely with OCT angiography over three cycles of antiangiogenic treatment. Outer retinal flow index, CNV flow area and central macular retinal thickness were measured. RESULTS: Quantitative measurements of CNV flow area and flow index showed rapid shutdown of flow over the initial 2 weeks, followed by reappearance of CNV channel by the fourth week, preceding fluid reaccumulation at 6 weeks. CONCLUSION: Frequent OCT angiography reveals a previously unknown pattern of rapid shutdown and reappearance of CNV channels within treatment cycles. OCT angiographic changes precede fluid reaccumulation and could be useful as leading indicators of CNV activity that could guide treatment timing. Further studies using OCT angiography in short intervals between antiangiogenic treatments are needed.

Retinal blood flow in glaucomatous eyes with single-hemifield damage.

PURPOSE: To examine the hypotheses that in glaucomatous eyes with single-hemifield damage, retinal blood flow (RBF) is significantly reduced in the retinal hemisphere corresponding with the abnormal visual hemifield and that there are significant associations among reduced retinal sensitivity (RS) in the abnormal hemifield, RBF, and structural measurements in the corresponding hemisphere. DESIGN: Prospective, nonrandomized, case-control study. PARTICIPANTS: Thirty eyes of 30 patients with glaucoma with visual field loss confined to a single hemifield and 27 eyes of 27 controls. METHODS: Normal and glaucomatous eyes underwent spectral-domain optical coherence tomography (SD-OCT) and standard automated perimetry. Doppler SD-OCT with a double-circle scanning pattern was used to measure RBF. The RBF was derived from the recorded Doppler frequency shift and the measured angle between the beam and the vessel. Total and hemispheric RBF, retinal nerve fiber layer (RNFL), and ganglion cell complex (GCC) values were calculated. The RS values were converted to 1/Lambert. Analysis of variance and regression analyses were performed. MAIN OUTCOME MEASURES: Total and hemispheric RS, RBF, RNFL, and GCC values. RESULTS: The total RBF (34.6±12.2 µl/minute) and venous cross-sectional area (0.039 ± 0.009 mm(2)) were reduced (P<0.001) in those with glaucoma compared with controls (46.5 ± 10.6 µl/minute; 0.052 ± 0.012 mm(2)). Mean RBF was reduced in the abnormal hemisphere compared with the opposite hemisphere (15.3 ± 5.4 vs. 19.3 ± 8.4 µl/minute; P = 0.004). The RNFL and GCC were thinner in the corresponding abnormal hemisphere compared with the opposite hemisphere (87.0 ± 20.2 vs. 103.7 ± 20.6 µm, P = 0.002; 77.6 ± 12.1 vs. 83.6 ± 10.1 µm, P = 0.04). The RBF was correlated with RNFL (r = 0.41; P = 0.02) and GCC (r = 0.43; P = 0.02) but not the RS (r = 0.31; P = 0.09) in the abnormal hemisphere. The RBF (19.3 ± 8.4 µl/minute), RNFL (103.7 ± 20.6 µm), and GCC (83.6 ± 10.1 µm) were reduced (P<0.05) in the hemisphere with apparently normal visual field in glaucomatous eyes compared with the mean hemispheric values of the normal eyes (23.2 ± 5.3 µl/minute, 124.8 ± 9.6 µm, and 96.1 ± 5.7 µm, respectively). CONCLUSIONS: In glaucomatous eyes with single-hemifield damage, the RBF is significantly reduced in the hemisphere associated with the abnormal hemifield. Reduced RBF is associated with thinner RNFL and GCC in the corresponding abnormal hemisphere. Reduced RBF and RNFL and GCC loss also are observed in the perimetrically normal hemisphere of glaucomatous eyes.

Quantitative optical coherence tomography angiography of choroidal neovascularization in age-related macular degeneration.

PURPOSE: To detect and quantify choroidal neovascularization (CNV) in patients with age-related macular degeneration (AMD) using optical coherence tomography (OCT) angiography. DESIGN: Observational, cross-sectional study. PARTICIPANTS: A total of 5 normal subjects and 5 subjects with neovascular AMD were included. METHODS: A total of 5 eyes with neovascular AMD and 5 normal age-matched controls were scanned by a high-speed (100 000 A-scans/seconds) 1050-nm wavelength swept-source OCT. The macular angiography scan covered a 3 × 3-mm area and comprised 200 × 200 × 8 A-scans acquired in 3.5 seconds. Flow was detected using the split-spectrum amplitude-decorrelation angiography (SSADA) algorithm. Motion artifacts were removed by 3-dimensional (3D) orthogonal registration and merging of 4 scans. The 3D angiography was segmented into 3 layers: inner retina (to show retinal vasculature), outer retina (to identify CNV), and choroid. En face maximum projection was used to obtain 2-dimensional angiograms from the 3 layers. The CNV area and flow index were computed from the en face OCT angiogram of the outer retinal layer. Flow (decorrelation) and structural data were combined in composite color angiograms for both en face and cross-sectional views. MAIN OUTCOME MEASURES: The CNV angiogram, CNV area, and CNV flow index. RESULTS: En face OCT angiograms of CNV showed sizes and locations that were confirmed by fluorescein angiography (FA). Optical coherence tomography angiography provided more distinct vascular network patterns that were less obscured by subretinal hemorrhage. The en face angiograms also showed areas of reduced choroidal flow adjacent to the CNV in all cases and significantly reduced retinal flow in 1 case. Cross-sectional angiograms were used to visualize CNV location relative to the retinal pigment epithelium and Bruch's layer and classify type I and type II CNV. A feeder vessel could be identified in 1 case. Higher flow indexes were associated with larger CNV and type II CNV. CONCLUSIONS: Optical coherence tomography angiography provides depth-resolved information and detailed images of CNV in neovascular AMD. Quantitative information regarding CNV flow and area can be obtained. Further studies are needed to assess the role of quantitative OCT angiography in the evaluation and treatment of neovascular AMD.

A Hybrid Deep Learning Classification of Perimetric Glaucoma Using Peripapillary Nerve Fiber Layer Reflectance and Other OCT Parameters from Three Anatomy Regions.

Précis: A hybrid deep-learning model combines NFL reflectance and other OCT parameters to improve glaucoma diagnosis. Objective: To investigate if a deep learning model could be used combine nerve fiber layer (NFL) reflectance and other OCT parameters for glaucoma diagnosis. Patients and Methods: This is a prospective observational study where of 106 normal subjects and 164 perimetric glaucoma (PG) patients. Peripapillary NFL reflectance map, NFL thickness map, optic head analysis of disc, and macular ganglion cell complex thickness were obtained using spectral domain OCT. A hybrid deep learning model combined a fully connected network (FCN) and a convolution neural network (CNN) to develop to combine those OCT maps and parameters to distinguish normal and PG eyes. Two deep learning models were compared based on whether the NFL reflectance map was used as part of the input or not. Results: The hybrid deep learning model with reflectance achieved 0.909 sensitivity at 99% specificity and 0.926 at 95%. The overall accuracy was 0.948 with 0.893 sensitivity and 1.000 specificity, and the AROC was 0.979, which is significantly better than the logistic regression models (p < 0.001). The second best model is the hybrid deep learning model w/o reflectance, which also had significantly higher AROC than logistic regression models (p < 0.001). Logistic regression with reflectance model had slightly higher AROC or sensitivity than the other logistic regression model without reflectance (p = 0.024). Conclusions: Hybrid deep learning model significantly improved the diagnostic accuracy, without or without NFL reflectance. Hybrid deep learning model, combining reflectance/NFL thickness/GCC thickness/ONH parameter, may be a practical model for glaucoma screen purposes.

Glaucomatous Focal Perfusion Loss in the Macula Measured by Optical Coherence Tomographic Angiography.

PURPOSE: To measure low perfusion area (LPA) and focal perfusion loss (FPL) in the macula using OCT angiography (OCTA) for glaucoma. DESIGN: Prospective, cross-sectional "case-control" comparison study. METHODS: A total of 60 patients with primary open-angle glaucoma (POAG) and 37 normal participants were analyzed. AngioVue 6 × 6-mm high-definition (400 × 400 transverse pixels) macular OCTA scans were performed on one eye of each participant. Flow signal was calculated using the split-spectrum amplitude-decorrelation angiography algorithm. En face ganglion cell layer plexus (GCLP) and superficial vascular complex (SVC) images were generated. Using custom software, vessel density (VD) maps were obtained by computing the fraction of area occupied by flow pixels after low-pass filtering by local averaging 41 × 41 pixels. LPA was defined by local VD below 0.5 percentile over a contiguous area above 98.5 percentile of the normal reference population. The FPL was the percent VD loss (relative to normal mean) integrated over the LPA. RESULTS: Among patients with POAG, 30 had perimetric and 30 had pre-perimetric glaucoma. The LPAGCLP-VD was 0.16±0.38 mm2 in normal and 5.78±6.30 mm2 in glaucoma subjects (P<0.001). The FPLGCLP-VD was 0.20%±0.47% in normal and 7.52%±8.84% in glaucoma subjects (P<0.001). The perimetric glaucoma diagnostic accuracy, measured by the area under the receiver operating curve, was 0.993 for LPAGCLP-VD and 0.990 for FPLGCLP-VD. The sensitivities were 96.7% and 93.3% at 95% specificity, respectively. The LPAGCLP-VD and FPLGCLP-VD had good repeatability (0.957 and 0.952 by intraclass correlation coefficient). Diagnostic accuracy was better than GCLP VD (AROC 0.950, sensitivity 83.3%) and OCT ganglion cell complex (GCC) thickness (AROC 0.927, sensitivity 80.0%), GCC focal loss volume (AROC 0.957, sensitivity 80.0%). The LPAGCLP-VD and FPLGCLP-VD correlated well with central VF mean deviations (Pearson's r=-0.716 and -0.705 respectively, both P<0.001). CONCLUSION: Assessment of macular focal perfusion loss using OCTA is useful in evaluating glaucomatous damage.

Sector-Based Regression Strategies to Reduce Refractive Error-Associated Glaucoma Diagnostic Bias When Using OCT and OCT Angiography.

Purpose: This cross-sectional study aimed to investigate the sectoral variance of optical coherence tomography (OCT) and OCT angiography (OCTA) glaucoma diagnostic parameters across eyes with varying degrees of refractive error. Methods: Healthy participants, including individuals with axial ametropia, enrolled in the Hong Kong FAMILY cohort were imaged using the Avanti/AngioVue OCT/OCTA system. The OCT and OCTA parameters obtained include peripapillary nerve fiber layer thickness (NFLT), peripapillary nerve fiber layer plexus capillary density (NFLP-CD), and macular ganglion cell complex thickness (GCCT). Sectoral measurements of NFLT, NFLP-CD, and GCCT were based on sectors and hemispheres. Results: A total of 1339 eyes from 791 participants were stratified based on spherical equivalent refraction: high myopia (<-6 D), low myopia (-6 D to -1 D), emmetropia (-1 D to 1 D), and hyperopia (>1 D). Multivariable broken stick regression models, accounting for age, sex, and signal strength, showed that all NFLT sectors except temporally, the inferior GCCT hemisphere, and half of the NFLP-CD sectors were more affected by ametropia-related covariates than the corresponding global parameters. As expected, the false-positive rates in those sectors were elevated. Finally, sector-specific axial length (AL) and spherical equivalent (SE) adjustments helped reduce the elevated false-positive rates. Conclusions: The effect of optical magnification is even more prominent among sectors than the global parameters. AL- and SE-based adjustments should be individualized to each sector to mitigate this magnification bias effectively. Translational Relevance: Identifying sectoral differences among diagnostic parameters and adopting these sector-based adjustments into commercial OCT systems will hopefully reduce false-positive rates related to refractive error.

Corneal epithelial thickness mapping by Fourier-domain optical coherence tomography in normal and keratoconic eyes.

OBJECTIVE: To map the corneal epithelial thickness with Fourier-domain optical coherence tomography (OCT) and to develop epithelial thickness-based variables for keratoconus detection. DESIGN: Cross-sectional observational study. PARTICIPANTS: One hundred forty-five eyes from 76 normal subjects and 35 keratoconic eyes from 22 patients. METHODS: A 26,000-Hz Fourier-domain OCT system with 5-µm axial resolution was used. The cornea was imaged with a Pachymetry + Cpwr scan pattern (6-mm scan diameter, 8 radials, 1024 axial-scans each, repeated 5 times) centered on the pupil. Three scans were obtained at a single visit in a prospective study. A computer algorithm was developed to map the corneal epithelial thickness automatically. Zonal epithelial thicknesses and 5 diagnostic variables, including minimum, superior-inferior (S-I), minimum-maximum (MIN-MAX), map standard deviation (MSD), and pattern standard deviation (PSD), were calculated. Repeatability of the measurements was assessed by the pooled standard deviation. The area under the receiver operating characteristic curve (AUC) was used to evaluate diagnostic accuracy. MAIN OUTCOME MEASURES: Descriptive statistics, repeatability, and AUC of the zonal epithelial thickness and diagnostic variables. RESULTS: The central, superior, and inferior epithelial thickness averages were 52.3 ± 3.6 µm, 49.6 ± 3.5 µm, and 51.2 ± 3.4 µm in normal eyes and 51.9 ± 5.3 µm, 51.2 ± 4.2 µm, and 49.1 ± 4.3 µm in keratoconic eyes. Compared with normal eyes, keratoconic eyes had significantly lower inferior (P = 0.03) and minimum (P<0.0001) corneal epithelial thickness, greater S-I (P = 0.013), more negative MIN-MAX (P<0.0001), greater MSD (P<0.0001), and larger PSD (P<0.0001). The repeatability of the zonal average, minimum, S-I, and MIN-MAX epithelial thickness variables were between 0.7 and 1.9 µm. The repeatability of MSD was better than 0.4 µm. The repeatability of PSD was 0.02 or better. Among all epithelial thickness-based variables investigated, PSD provided the best diagnostic power (AUC = 1.00). Using an PSD cutoff value of 0.057 alone gave 100% specificity and 100% sensitivity. CONCLUSIONS: High-resolution Fourier-domain OCT mapped corneal epithelial thickness with good repeatability in both normal and keratoconic eyes. Keratoconus was characterized by apical epithelial thinning. The resulting deviation from the normal epithelial pattern could be detected with very high accuracy using the PSD variable. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Split-spectrum amplitude-decorrelation angiography with optical coherence tomography.

Amplitude decorrelation measurement is sensitive to transverse flow and immune to phase noise in comparison to Doppler and other phase-based approaches. However, the high axial resolution of OCT makes it very sensitive to the pulsatile bulk motion noise in the axial direction. To overcome this limitation, we developed split-spectrum amplitude-decorrelation angiography (SSADA) to improve the signal-to-noise ratio (SNR) of flow detection. The full OCT spectrum was split into several narrower bands. Inter-B-scan decorrelation was computed using the spectral bands separately and then averaged. The SSADA algorithm was tested on in vivo images of the human macula and optic nerve head. It significantly improved both SNR for flow detection and connectivity of microvascular network when compared to other amplitude-decorrelation algorithms.

Volumetric directional optical coherence tomography.

Photoreceptor loss and resultant thinning of the outer nuclear layer (ONL) is an important pathological feature of retinal degenerations and may serve as a useful imaging biomarker for age-related macular degeneration. However, the demarcation between the ONL and the adjacent Henle's fiber layer (HFL) is difficult to visualize with standard optical coherence tomography (OCT). A dedicated OCT system that can precisely control and continuously and synchronously update the imaging beam entry points during scanning has not been realized yet. In this paper, we introduce a novel imaging technology, Volumetric Directional OCT (VD-OCT), which can dynamically adjust the incident beam on the pupil without manual adjustment during a volumetric OCT scan. We also implement a customized spoke-circular scanning pattern to observe the appearance of HFL with sufficient optical contrast in continuous cross-sectional scans through the entire volume. The application of VD-OCT for retinal imaging to exploit directional reflectivity properties of tissue layers has the potential to allow for early identification of retinal diseases.

Effect of algorithms and covariates in glaucoma diagnosis with optical coherence tomography angiography.

PURPOSE: To assess the effects of algorithms and covariates in glaucoma diagnosis with optical coherence tomography angiography (OCTA). METHODS: In this prospective cross-sectional study, one eye each of 36 normal controls and 64 patients with glaucoma underwent 4.5 mm disc-centred and 6 mm macula-centred OCTA scans. The peripapillary nerve fibre layer plexus capillary density (NFLP-CD) and macular superficial vascular complex vessel density (SVC-VD) were measured using both a commercial algorithm (AngioAnalytics) and a custom algorithm (Center for Ophthalmic Optics & Lasers Angiography Reading Toolkit (COOL-ART)). The nerve fibre layer and ganglion cell complex thicknesses were measured on structural OCT. RESULTS: The overall peripapillary NFLP-CD and macular SVC-VD measured with the two algorithms were highly correlated but poorly agreed. Among the normal controls, the perfusion measurements made by both algorithms were significantly correlated with age. AngioAnalytics measurements were also correlated with signal strength index, while COOL-ART measurements were not. These covariates were adjusted. The diagnostic accuracy, measured as the area under the receiver operating characteristic curve for glaucoma detection, was not significantly different between algorithms, between structural and perfusion parameters and between the peripapillary and macular regions (All p>0.05). The macular SVC-VD in the 6 mm square had a significantly higher diagnostic accuracy than that of the central 3 mm square area (p=0.005). CONCLUSIONS: AngioAnalytics and COOL-ART vessel density measurements are not interchangeable but potentially interconvertible. Age and signal strength are significant covariates that need to be considered. Both algorithms and both peripapillary and macular perfusion parameters have similarly good diagnostic accuracy comparable to structural OCT. A larger macular analytic area provides higher diagnostic accuracy.

Regression-Based Strategies to Reduce Refractive Error-Associated Glaucoma Diagnostic Bias When Using OCT and OCT Angiography.

Purpose: The purpose of this study was to correct refractive error-associated bias in optical coherence tomography (OCT) and OCT angiography (OCTA) glaucoma diagnostic parameters. Methods: OCT and OCTA imaging were obtained from participants in the Hong Kong FAMILY cohort. The Avanti/AngioVue OCT/OCTA system was used to measure the peripapillary nerve fiber layer thickness (NFLT), peripapillary nerve fiber layer plexus capillary density (NFLP-CD), macular ganglion cell complex thickness (GCCT), and macular superficial vascular complex vascular density (SVC-VD). Healthy eyes, including ones with axial ametropia, were enrolled for analysis. Results: A total of 1346 eyes from 792 participants were divided into 4 subgroups: high myopia (<-6D), low myopia (-6D to -1D), emmetropia (-1D to 1D), and hyperopia (>1D). After accounting for age, sex, and signal strength, multivariable regression showed strong dependence in most models for NFLT, GCCT, and NFLP-CD on axial eye length (AL), spherical equivalent (SE) refraction, and apparent optic disc diameter (DD). Optical analysis indicated that AL-related transverse optical magnification variations predominated over anatomic variations and were responsible for these trends. Compared to the emmetropic group, the false positive rates were significantly (Chi-square test P < 0.003) elevated in both myopia groups for NFLT, NFLP-CD, and GCCT. Regression-based adjustment of these diagnostic parameters with AL or SE significantly (McNemar test P < 0.03) reduced the elevated false positive rates. Conclusions: Myopic eyes are biased to have lower NFLT, GCCT, and NFLP-CD measurements. AL- and SE-based adjustments were effective in mitigating this bias. Translational Relevance: Adoption of these adjustments into commercial OCT systems may reduce false positive rates related to refractive error.

Focal Loss Analysis of Nerve Fiber Layer Reflectance for Glaucoma Diagnosis.

Purpose: To evaluate nerve fiber layer (NFL) reflectance for glaucoma diagnosis. Methods: Participants were imaged with 4.5 × 4.5 mm volumetric disc scans using spectral-domain optical coherence tomography. The normalized NFL reflectance map was processed by an azimuthal filter to reduce directional reflectance bias caused by variation of beam incidence angle. The peripapillary area of the map was divided into 160 superpixels. Average reflectance was the mean of superpixel reflectance. Low-reflectance superpixels were identified as those with NFL reflectance below the fifth percentile normative cutoff. Focal reflectance loss was measured by summing loss in low-reflectance superpixels. Results: Thirty-five normal, 30 preperimetric, and 35 perimetric glaucoma participants were enrolled. Azimuthal filtering improved the repeatability of the normalized NFL reflectance, as measured by the pooled superpixel standard deviation (SD), from 0.73 to 0.57 dB (P < 0.001, paired t-test) and reduced the population SD from 2.14 to 1.78 dB (P < 0.001, t-test). Most glaucomatous reflectance maps showed characteristic patterns of contiguous wedge or diffuse defects. Focal NFL reflectance loss had significantly higher diagnostic sensitivity than the best NFL thickness parameter (from map or profile): 77% versus 55% (P < 0.001) in glaucoma eyes with the specificity fixed at 99%. Conclusions: Azimuthal filtering reduces the variability of NFL reflectance measurements. Focal NFL reflectance loss has excellent glaucoma diagnostic accuracy compared to the standard NFL thickness parameters. The reflectance map may be useful for localizing NFL defects. Translational Relevance: The high diagnostic accuracy of NFL reflectance may make population-based screening feasible.

Prospective evaluation of optical coherence tomography for disease detection in the Casey mobile eye clinic.

This study was designed to evaluate iVue Spectral-domain optical coherence tomography (SD-OCT) effectiveness in screening for eye disease compared to clinical examination. Subjects were recruited from the Casey Eye Community Outreach Program Mobile Clinic during its routinely scheduled outreach clinics to indigent, underserved populations throughout Oregon. Macular optical coherence tomography interpretation and automated optical coherence tomography analysis were compared to the clinical examination, with specific attention to findings indicative of retinal abnormalities, risks for glaucoma, and narrow angles. As a result, a total of 114 subjects were included in this study. In diabetics, optical coherence tomography and clinical exam were in fair agreement (kappa = 0.39), with 22% of eyes having abnormal findings on macular optical coherence tomography and 26% of eyes having diabetic retinopathy or diabetic macular edema on fundus exam. In non-diabetics, optical coherence tomography and clinical exam were in fair agreement (kappa = 0.28), with 11% of eyes having abnormal findings on macular optical coherence tomography and 9% on fundus exam. Using optical coherence tomography ganglion cell complex and retinal nerve fiber layer analysis, 18% of eyes were found to be glaucoma suspects, whereas clinical exam of cup-to-disc ratio detected 8% and intraocular pressure 5%. Agreements between optical coherence tomography and other methods were poor (kappa < 0.11) for glaucoma suspect. Anterior segment optical coherence tomography of the angle found 8% of eyes to have occludable angles, whereas slit lamp and gonioscopy found 5% of eyes to have narrow angles, with moderate agreement (kappa = 0.57). In summary, optical coherence tomography detected additional retinal abnormalities, glaucoma suspects, and narrow angles compared to clinical exam alone and may serve as a useful adjunct to the clinical exam in screening for eye disease in a low-risk, medically underserved, ethnically diverse population.

Relationship Between Macular Vessel Density and Total Retinal Blood Flow in Primary Open-angle Glaucoma.

PRECIS: An association between macular vessel density (VD) and total retinal blood flow (TRBF) was demonstrated in subjects with primary open-angle glaucoma (POAG) and visual field (VF) loss. PURPOSE: The purpose of this study was to report relationships of macular VD metrics and TRBF in POAG. MATERIALS AND METHODS: A total of 24 POAG and 19 healthy control subjects participated in the study. Subjects underwent optical coherence tomography and angiography for measurements of inner retinal thickness (IRT), VD, and spacing between large vessels (SLV) and small vessels (SSV). Doppler optical coherence tomography imaging was performed for TRBF measurement. In POAG subjects, automated perimetry was performed and VF loss expressed as mean deviation was measured. RESULTS: Compared with the control group, POAG group had decreased VD, TRBF, IRT, and increased SLV (P<0.0001). Decreased VD (Pearson correlation, r=0.51; P<0.0001; N=43) and increased SLV (Spearman correlation, rs=-0.47; P=0.001) were correlated with decreased TRBF. Decreased VD and SSV (r≥0.39; P≤0.001; N=43) and increased SLV (rs=-0.71; P<0.0001) were associated with decreased IRT. Decreased VF mean deviation was correlated with decreased VD, SSV, IRT (r≥0.53; P≤0.001; N=24), and with increased SLV (rs=-0.84; P<0.0001). CONCLUSIONS: The finding of an association between macular VD and TRBF supports the role of vascular factors in the pathophysiology of POAG and potential conduct of future studies aimed at identifying multiple image-based vascular metrics for disease diagnosis.

Optical coherence tomographic angiography study of perfusion recovery after surgical lowering of intraocular pressure.

We investigated the time and location of retinal perfusion recovery after surgical intraocular pressure (IOP) lowering in glaucoma by using optical coherent tomography angiography (OCTA). Seventeen patients were analyzed. The 4.5 × 4.5-mm OCTA scans centered on the disc were performed preoperatively and postoperatively at 6 weeks, 3 months, and 6 months. The peripapillary retinal nerve fiber layer (NFL) thickness, NFL plexus capillary density (NFLP-CD) and visual field (VF) were measured overall and in 8 corresponding sectors. The low-perfusion area (LPA) was used to assess the cumulative area where local NFLP-CD was significantly below normal. At 6 months, the average IOP decreased 5.3 mmHg (P = 0.004), LPA decreased by 15% (P = 0.005), and NFLP-CD improved by 12% (P < 0.001). The NFL thickness and VF mean deviation didn't change significantly at any time point. Among the sectors with significant preoperative NFLP-CD loss, the recovery at 6 months was greatest in sectors with minimal preoperative NFL thinning (P < 0.001). In conclusion, surgical IOP lowering may improve NFLP capillary perfusion after 6 months. The perfusion recovery tended to occur in areas with minimal NFL thinning at baseline. OCTA parameters may have potential usefulness as pharmacodynamic biomarkers for glaucoma therapy.

Relating retinal blood flow and vessel morphology in sickle cell retinopathy.

PURPOSE: The purpose of the current study was to determine associations between retinal blood flow and vessel morphology metrics in sickle cell retinopathy (SCR) and healthy normal control (NC) subjects. METHODS: Optical coherence tomography angiography (OCTA) and Doppler OCT imaging were performed in 12 SCR (15 eyes) and 19 NC (26 eyes) subjects. Vessel tortuosity was measured using a dedicated image analysis algorithm applied to OCTA images. Vessel density and spacing between vessels were determined from OCTA images by a fractal dimension analysis method. Retinal blood flow was quantified using a phase-resolved technique applied to en face Doppler OCT images. RESULTS: There was a significant association between increased retinal blood flow and increased vessel tortuosity (P = 0.03). Furthermore, increased retinal blood flow was associated with increased vessel density (P = 0.03) and decreased spacing between small vessels (P = 0.01). There was no significant association between retinal blood flow and spacing between large vessels (P = 0.11). Vessel tortuosity and blood flow were increased, whereas spacing between small vessels was decreased in SCR compared to NC group (P ≤ 0.03). There were no significant differences in vessel density or spacing between large vessels between the SCR and NC groups (P ≥ 0.31). CONCLUSIONS: Associations between retinal hemodynamics and vessel morphology were reported, providing better understanding of retinal pathophysiology and insight into potential quantitative biomarkers to evaluate SCR.

Sectorwise Visual Field Simulation Using Optical Coherence Tomographic Angiography Nerve Fiber Layer Plexus Measurements in Glaucoma.

PURPOSE: To simulate 24-2 visual field (VF) using optical coherence tomographic angiography (OCTA) for glaucoma evaluation. DESIGN: Cross-sectional study. METHODS: One eye each of 39 glaucoma and 31 age-matched normal participants was scanned using 4.5-mm OCTA scans centered on the disc. The peripapillary retinal nerve fiber layer plexus capillary density (NFLP-CD, %area) was measured. The NFLP-CD and 24-2 VF maps were divided into 8 corresponding sectors using an extension of Garway-Heath scheme. RESULTS: Sector NFLP-CD was transformed to a logarithmic dB scale and converted to sector simulated VF deviation maps. Comparing simulated and actual 24-2 VF maps, the worst sector was in the same or adjacent location in the same hemisphere 97% of the time. VF mean deviation (VF-MD) was simulated by NFLP mean deviation (NFLP-MD). The differences between NFLP-MD and VF-MD in early, moderate, and severe glaucoma stages were -0.9 ± 2.0, 0.9 ± 2.9, and 5.8 ± 3.2 dB. NFLP-MD had better (P = .015) between-visit reproducibility (0.63 dB pooled standard deviation) than VF-MD (1.03 dB). NFLP-MD had a significantly higher sensitivity than VF-MD (P < .001) and overall NFL thickness (P = .031). CONCLUSIONS: OCTA-based simulated VF agreed well with actual 24-2 VF in terms of both the location and severity of glaucoma damage, with the exception of severe glaucoma in which the simulation tended to underestimate severity. The NFLP-MD had better reproducibility than actual VF-MD and holds promise for improving glaucoma monitoring. The NFLP-MD had better diagnostic accuracy than both VF-MD and overall NFL thickness and may be useful for early glaucoma diagnosis.

Detection of macular ganglion cell loss in glaucoma by Fourier-domain optical coherence tomography.

PURPOSE: To map ganglion cell complex (GCC) thickness with high-speed Fourier-domain optical coherence tomography (FD-OCT) and compute novel macular parameters for glaucoma diagnosis. DESIGN: Observational, cross-sectional study. PARTICIPANTS: One hundred seventy-eight participants in the Advanced Imaging for Glaucoma Study, divided into 3 groups: 65 persons in the normal group, 78 in the perimetric glaucoma group (PG), and 52 in the preperimetric glaucoma group (PPG). METHODS: The RTVue FD-OCT system was used to map the macula over a 7 x 6 mm region. The macular OCT images were exported for automatic segmentation using software we developed. The program measured macular retinal (MR) thickness and GCC thickness. The GCC was defined as the combination of nerve fiber, ganglion cell, and inner plexiform layers. Pattern analysis was applied to the GCC map and the diagnostic powers of pattern-based diagnostic parameters were investigated. Results were compared with time-domain (TD) Stratus OCT measurements of MR and circumpapillary nerve fiber layer (NFL) thickness. MAIN OUTCOME MEASURES: Repeatability was assessed by intraclass correlation, pooled standard deviation, and coefficient of variation. Diagnostic power was assessed by the area under the receiver operator characteristic (AROC) curve. Measurements in the PG group were the primary measures of performance. RESULTS: The FD-OCT measurements of MR and GCC averages had significantly better repeatability than TD-OCT measurements of MR and NFL averages. The FD-OCT GCC average had significantly (P = 0.02) higher diagnostic power (AROC = 0.90) than MR (AROC = 0.85 for both FD-OCT and TD-OCT) in differentiating between PG and normal. One GCC pattern parameter, global loss volume, had significantly higher AROC (0.92) than the overall average (P = 0.01). The diagnostic powers of the best GCC parameters were statistically equal to TD-OCT NFL average. CONCLUSIONS: The higher speed and resolution of FD-OCT improved the repeatability of macular imaging compared with standard TD-OCT. Ganglion cell mapping and pattern analysis improved diagnostic power. The improved diagnostic power of macular GCC imaging is on par with, and complementary to, peripapillary NFL imaging. Macular imaging with FD-OCT is a useful method for glaucoma diagnosis and has potential for tracking glaucoma progression.