Ahmed M. Hagag

Optical coherence tomography angiography: Technical principles and clinical applications in ophthalmology

Optical coherence tomography angiography (OCTA) is a functional extension of OCT that provides information on retinal and choroidal circulations without the need for dye injections. With the recent development of high-speed OCT systems and efficient algorithms, OCTA has become clinically feasible. In this review article, we discuss the technical principles of OCTA, including image processing and artifacts, and its clinical applications in ophthalmology. We summarize recent studies which qualitatively or quantitatively assess disease presentation, progression, and/or response to treatment.

Automated detection of preserved photoreceptor on optical coherence tomography in choroideremia based on machine learning

Optical coherence tomography (OCT) can demonstrate early deterioration of the photoreceptor integrity caused by inherited retinal degeneration diseases (IRDs). A machine learning method based on random forests was developed to automatically detect continuous areas of preserved ellipsoid zone structure (an easily recognizable part of the photoreceptors on OCT) in 16 eyes of patients with choroideremia (a type of IRD). Pseudopodial extensions protruding from the preserved ellipsoid zone areas are detected separately by a local active contour routine. The algorithm is implemented on en face images with minimum segmentation requirements, only needing delineation of the Bruchs membrane, thus evading the inaccuracies and technical challenges associated with automatic segmentation of the ellipsoid zone in eyes with severe retinal degeneration.

Evaluation of Automatically Quantified Foveal Avascular Zone Metrics for Diagnosis of Diabetic Retinopathy Using Optical Coherence Tomography Angiography

Purpose To describe an automated algorithm to quantify the foveal avascular zone (FAZ), using optical coherence tomography angiography (OCTA), and to compare its performance for diagnosis of diabetic retinopathy (DR) and association with best-corrected visual acuity (BCVA) to that of extrafoveal avascular area (EAA). Methods We obtained 3 × 3-mm macular OCTA scans in diabetic patients with various levels of DR and healthy controls. An algorithm based on a generalized gradient vector flow (GGVF) snake model detected the FAZ, and metrics assessing FAZ size and irregularity were calculated. We compared the automated FAZ segmentation to manual delineation and tested the within-visit repeatability of FAZ metrics. The correlations of two conventional FAZ metrics, two novel FAZ metrics, and EAA with DR severity and BCVA, as determined by Early Treatment Diabetic Retinopathy Study (ETDRS) charts, were assessed. Results Sixty-six eyes from 66 diabetic patients and 19 control eyes from 19 healthy participants were included. The agreement between manual and automated FAZ delineation had a Jaccard index > 0.82, and the repeatability of automated FAZ detection was excellent in eyes at all levels of DR severity. FAZ metrics that incorporated both FAZ size and shape irregularity had the strongest correlation with clinical DR grade and BCVA. Of all the tested OCTA metrics, EAA had the greatest sensitivity in differentiating diabetic eyes without clinical evidence of retinopathy, mild to moderate nonproliferative DR (NPDR), and severe NPDR to proliferative DR from healthy controls. Conclusions The GGVF snake algorithm tested in this study can accurately and reliably detect the FAZ, using OCTA data at all DR severity grades, and may be used to obtain clinically useful information from OCTA data regarding macular ischemia in patients with diabetes. While FAZ metrics can provide clinically useful information regarding macular ischemia, and possibly visual acuity potential, EAA measurements may be a better biomarker for DR.

Assessing total retinal blood flow in diabetic retinopathy using multiplane en face Doppler optical coherence tomography

Aim To assess total retinal blood flow (TRBF) in diabetic retinopathy (DR) using multiplane en face Doppler optical coherence tomography (OCT). Methods A 70 kHz spectral-domain OCT system scanned a 2×2 mm area centred at the optic disc of the eyes with DR and healthy participants. The multiplane en face Doppler OCT algorithm generated a three-dimensional volumetric data set consisting of 195 en face planes. The TRBF was calculated from the maximum flow values of each branching retinal vein at an optimised en face plane. DR severity was graded according to the international clinical classification system. The generalised linear model method was used to compare flow values between DR groups and the control group. Results A total of 71 eyes from 71 participants were included. Ten eyes were excluded due to poor image quality. The within-visit repeatability of scans was 4.1% (coefficient of variation). There was no significant difference in the TRBF between the healthy (46.7±10.2 µL/min) and mild/moderate non-proliferative DR (44.9±12.6 µL/min) groups. The TRBF in severe non-proliferative DR (39.1±12.6 µL/min) and proliferative DR (28.9±8.85 µL/min) groups were significantly lower (p=0.04 and p<0.0001, respectively) than that of the healthy group. TRBF was correlated with DR disease severity (p<0.0001, linear trend test). Conclusion The novel multiplane en face Doppler OCT method provided reliable measurements of TRBF in DR eyes. This may be a useful tool in understanding the pathophysiology of DR.

OCT Angiography Changes in the 3 Parafoveal Retinal Plexuses in Response to Hyperoxia

Purpose Use projection-resolved OCT angiography to investigate the autoregulatory response in the 3 parafoveal retinal plexuses under hyperoxia. Design Prospective cohort study. Participants Nine eyes from 9 healthy participants. Methods One eye from each participant was scanned using a commercial spectral-domain OCT system. Two repeated macular scans (3 × 3 mm2) were acquired at baseline and during oxygen breathing. The split-spectrum amplitude-decorrelation algorithm was used to detect blood flow. The projection-resolved algorithm was used to suppress projection artifacts and resolve blood flow in 3 distinct parafoveal plexuses. The Wilcoxon signed-rank test was used to compare baseline and hyperoxic parameters. The coefficient of variation, intraclass correlation coefficient, and pooled standard deviation were used to assess the reliability of OCT angiography measurements. Main Outcome Measures Flow index and vessel density were calculated from the en face angiograms of each of the 3 plexuses, as well as from the all-plexus inner retinal slab. Results Hyperoxia induced significant reduction in the flow index (-11%) and vessel density (-7.8%) of only the deep capillary plexus (P < 0.001) and in the flow index of the all-plexus slab (P = 0.015). The flow index also decreased in the intermediate capillary plexus and the superficial vascular complex, but these changes were small and not statistically significant. The projection-resolved OCT angiography showed good within-session baseline repeatability (coefficient of variation, 0.8%-5.2%; intraclass correlation coefficient, 0.93-0.98) in all parameters. Relatively large between-day response reproducibility was observed (pooled standard deviation, 1.7%-9.4%). Conclusions Projection-resolved OCT angiography was able to show that the retinal autoregulatory response to hyperoxia affects only the deep capillary plexus, but not the intermediate capillary plexus or superficial vascular complex.

Automated Quantification of Nonperfusion Areas in 3 Vascular Plexuses With Optical Coherence Tomography Angiography in Eyes of Patients With Diabetes

Importance Diabetic retinopathy (DR) is a leading cause of vision loss that is managed primarily through qualitative clinical examination of the retina. Optical coherence tomography angiography (OCTA) may offer an objective and quantitative method of evaluating DR. Objective To quantify capillary nonperfusion in 3 vascular plexuses in the macula of eyes patients with diabetes of various retinopathy severity using projection-resolved OCTA (PR-OCTA). Design, Setting, and Participants Cross-sectional study at a tertiary academic center comprising 1 eye each from healthy control individuals and patients with diabetes at different severity stages of retinopathy. Data were acquired and analyzed between January 2015 and December 2017. Main Outcomes and Measures Foveal avascular zone area, extrafoveal avascular area (EAA), and the sensitivity of detecting levels of retinopathy. Results The study included 39 control individuals (20 women [51%]; mean [SD] age, 43.41 [19.37] years); 16 patients with diabetes without retinopathy (8 women [50%]; mean [SD] age, 56.50 [12.43] years); 23 patients with mild to moderate nonproliferative DR (18 women [78%] ; mean [SD] age, 62.48 [10.55] years); and 32 patients with severe nonproliferative DR or proliferative DR (12 women [38%]; mean age, 53.41 [14.05] years). Mean (SD) foveal avascular zone area was 0.203 (0.103) mm2 for control individuals, 0.192 (0.084) mm2 for patients with diabetes without retinopathy, 0.243 [0.079] mm2 for mild to moderate nonproliferative DR, and 0.359 (0.275) mm2 for severe nonproliferative DR or proliferative DR. Mean (SD) EAA in whole inner retinal slab in these groups, respectively, were 0.020 (0.031) mm2, 0.034 (0.047) mm2, 0.038 (0.040) mm2, and 0.237 (0.235) mm2. The mean (SD) sum of EAA from 3 segmented plexuses in each of the respective groups were 0.103 (0.169) mm2, 0.213 (0.242) mm2, 0.451 (0.243) mm2, and 1.325 (1.140) mm2. With specificity fixed at 95%, using EAA in inner retinal slab, the sensitivity of detecting patients with diabetes from healthy control individuals was 28% (95% CI, 18%-40%), 31% for patients with DR (95% CI, 19%-45%), and 47% for patients with severe DR (95% CI, 29%-65%) from whole inner retinal EAA. With the sum of EAA from 3 individual plexuses, the sensitivities were 69% (95% CI, 57%-80%), 82% (95% CI, 70%-91%), and 97% (95% CI, 85%-100%), respectively. Avascular areas were not associated with signal strength index. The commercial vessel density from the 2-plexus scheme distinguished the groups with lower sensitivity and were dependent on SSI. Conclusions and Relevance Automatically quantified avascular areas from a 3-layer segmentation scheme using PR-OCTA distinguished levels of retinopathy with a greater sensitivity than avascular areas from unsegmented inner retinal slab or measurements from a commercially available vessel density in 2-layer scheme. Additional studies are needed to investigate the applicability of nonperfusion parameters in clinical settings.

Quantitative Evaluation of Choroidal Neovascularization under Pro Re Nata Anti–Vascular Endothelial Growth Factor Therapy with OCT Angiography

Purpose To use optical coherence tomography angiography (OCTA) derived quantitative metrics to assess the response of choroidal neovascularization to pro-re-nata (PRN) anti-endothelial growth factor (anti-VEGF) treatment in neovascular age-related macular degeneration (AMD). Design Prospective longitudinal cohort study. Participants Fourteen eyes from 14 study participants with treatment-naïve neovascular AMD were enrolled. Methods Subjects were evaluated monthly and treated with intravitreal anti-VEGF agents under a PRN protocol for one year. At each visit, two 3×3 mm2 OCTA scans were obtained. Custom image processing was applied to segment the outer retinal slab, suppress projection artifact, and automatically detect CNV. CNV membrane area (mm2) and CNV vessel area (mm2) was calculated. Main Outcomes Individual and mean CNV membrane area and CNV vessel area at each visit; within-visit repeatability determined by coefficient of variation. Results Eight eyes had entire CNV within 3×3 mm2 scanning area and had adequate image quality for CNV quantification. One case (case #2) was excluded from analysis due to the presence of a large subretinal hemorrhage overlying the CNV membrane. In the remaining cases, CNV vessel area was reduced by 39%, 50%, 43%, and 41% at months 1, 3, 6, and 12 respectively. CNV membrane area was reduced by 39%, 51%, 54%, and 45% at months 1, 3, 6, and 12. At month 6, mean change from baseline was not statistically significant for CNV vessel area, while it was statistically significant for CNV membrane area. Neither metric was significantly different compared to baseline at month 12. Individual analyses revealed each CNV had a unique response under PRN treatment. Within-visit repeatability was was 7.96% (coefficient of variation) for CNV vessel area and 7.37% for CNV membrane area. Conclusions In this small exploratory study of CNV response to PRN anti-VEGF treatment, both CNV vessel area and membrane area were reduced compared to baseline after three months. After one year of follow-up, these reductions were no longer statistically significant. When anti-VEGF treatment was held, increasing CNV vessel area over time often resulted in exudation, but it was not possible to exactly when exudation occurs.

Automated drusen detection in dry age-related macular degeneration by multiple-depth, en face optical coherence tomography

We introduce a method to automatically detect drusen in dry age-related macular degeneration (AMD) from optical coherence tomography with minimum need for layer segmentation. The method is based on the en face detection of drusen areas in C-scans at certain distances above the Bruchs membrane, circumventing the difficult task of pathologic retinal pigment epithelium segmentation. All types of drusen can be detected, including the challenging subretinal drusenoid deposits (pseudodrusen). The high sensitivity and accuracy demonstrated here shows its potential for detection of drusen onset in early AMD.