Systematic Evaluation of Optical Coherence Tomography Angiography in Retinal Vein Occlusion




Purpose


To evaluate the clinical utility of optical coherence tomography angiography (OCTA) in patients with retinal vein occlusion (RVO), and to systematically compare OCTA images with changes seen on color fundus photography and fluorescein angiography (FA).


Design


Reliability analysis.


Methods


Eighty-one eyes of 76 patients with a history of RVO (branch, central, or hemicentral), both acute and chronic, underwent OCTA and color fundus photography. In 29 eyes, data were compared to FA imaging. Comparative and multimodal analysis of the 3 imaging procedures were performed.


Results


We identified good agreement between FA and OCTA scans centered on the macula for capillary nonperfusion (intraclass correlation coefficient [ICC] 0.825 for the 3 × 3-mm scan and 0.891 for the 8 × 8-mm scan). Agreement for area of capillary changes (dilation, pruning, and telangiectasia) was also substantial (ICC 0.712 for the 3 × 3-mm scan and 0.787 for the 8 × 8-mm scan). For foveal avascular zone grading, agreement was good for the 3 × 3-mm scan (kappa = 1.000 for radius and kappa = 0.799 for outline) but poor for the 8 × 8-mm scan (kappa = 0.156 for radius and kappa = 0.600 for outline). The quality of the images obtained was an important issue for OCTA, as 15.1% of scans were nongradable, particularly in patients unable to maintain fixation.


Conclusions


OCTA is a quick, reliable, and noninvasive method to evaluate the area of capillary nonperfusion and foveal avascular zone morphology in patients with RVO. However, good fixation is a requirement for acquisition of good-quality images.


Retinal vein occlusion (RVO) is a common retinal vascular disease and an important cause of visual loss worldwide. For a correct diagnosis and management of vision-threatening complications, such as capillary nonperfusion, macular edema (ME), and neovascularization, imaging studies of the retina are usually warranted. Currently, fluorescein angiography (FA) is the standard method to detect areas of retinal nonperfusion and neovascularization. However, FA is an invasive and time-consuming procedure that can cause nausea and, rarely, an allergic reaction with anaphylaxis. Also, FA images are 2-dimensional and do not allow separate visualization of the superficial and deeper layers of the retinal vasculature.


In recent years, optical coherence tomography (OCT) has become widely available as a noninvasive method providing structural imaging of the retina. A recent advance of this technique is OCT angiography (OCTA), which allows the visualization of 3-dimensional vascular maps of the retina. The first commercially available OCTA system (using the AngioVue software on the RTVue XR Avanti Spectral-Domain OCT [Optovue Inc, Fremont, California, USA]) uses the split-spectrum amplitude decorrelation angiography (SSADA) algorithm to detect motion of erythrocytes in the blood vessel lumen by measuring the variation in reflected OCT signal amplitude between consecutive cross-sectional B-scans, generating high-quality angiograms of the retina and the choroid. Previous studies using this system have been able to detect chorioretinal vascular lesions in a number of retinal diseases.


Few studies, so far, have analyzed the use of OCTA in the detection and quantification of retinal nonperfusion. In this reliability study, we evaluated the ability of OCTA to correctly visualize the pathologic changes associated with RVO, including retinal nonperfusion, neovascularization, and changes to the foveal avascular zone (FAZ), and test its ability to substitute for FA in certain clinical scenarios.


Methods


All patients with RVO that attended the medical retina clinics at Moorfields Eye Hospital and underwent OCTA from October 9, 2014, through May 15, 2015 were included in the study. Approval for data collection and analysis was obtained from the Institutional Review Board of Moorfields Eye Hospital, and adhered to the tenets set forth in the Declaration of Helsinki.


Patient demographic and clinical data were obtained from the patients’ electronic medical records. Fundus photographs and FA were acquired with digital retinal camera systems (Topcon 3D OCT-2000 [Topcon Medical Systems, Oakland, New Jersey, USA], Topcon TRC 50IX [Topcon Medical Systems], Optos 200Tx [Optos plc, Dunfermline, Scotland, UK] and Spectralis HRA + OCT [Heidelberg Engineering, Heidelberg, Germany]) and were extracted for grading. Fundus photographs and FAs were graded if they were done within 4 weeks of OCTA. For the 10 color fundus photographs and the 6 FAs that were not done on the same day as OCTA, a thorough evaluation and comparison of the images and medical records was undertaken to exclude any patients that had any vascular events (eg, ischemic conversion or new occlusion) or if ME developed between the 2 scans. In these patients, 1 intravitreal injection of anti–vascular endothelial growth factor (VEGF) was allowed between the 2 scans, but the data were not used to evaluate neovascularization or ME.


Grading of Fundus Photographs and Fluorescein Angiography


Grading protocols for fundus photographs and FA were adapted from the Central Vein Occlusion Study (CVOS) Group, the Branch Vein Occlusion Study (BVOS) Group, the Standard Care vs Corticosteroid for Retinal Vein Occlusion (SCORE), and the Early Treatment of Diabetic Retinopathy Study (ETDRS). Grading was designed to provide qualitative and quantitative assessment of fundus photography and angiographic endpoints. For each modality, image quality was classified as “adequate” when photographic features could be read with confidence, “fair” when all or nearly all photographic features could be read but confidence in grading was only fair, and “poor” when no photographic features could be read with confidence owing to poor image quality.


Color fundus photographs were evaluated for presence and area of intraretinal hemorrhage (IRH) as well as presence of other features of vein occlusion, including dilated retinal veins, ghost vessels, intraretinal cystoid spaces, hard exudates, epiretinal membrane, subretinal fibrosis, photocoagulation scars, cotton-wool spots, pigmentary changes, collateral vessels, neovascularization elsewhere (NVE), preretinal or vitreous hemorrhage, and vitreous hemorrhage, as well as disc swelling or disc neovascularization (NVD) ( Supplemental Figure 1 , available at AJO.com ).


For FA, the area of fluorescein leakage, area of capillary nonperfusion, and area of capillary changes (dilation of capillaries or arteriolar abnormalities such as pruning) were quantified. Other features evaluated on FA included FAZ size and outline, presence of collaterals, and presence of NVD (originating and residing within 1 disc diameter of the disc margin) and/or NVE. A single early- to mid-phase image centered on the macula was selected for analysis of areas of ischemia and FAZ. A late-phase image was chosen for analysis of leakage and neovascularization. The area of IRH, fluorescein leakage, capillary nonperfusion, and capillary changes were calculated in disc areas (DA) based on the ETDRS grid centered on the macula. The grid had a foveal central subfield, a middle ring, and an outer ring (each corresponding to a circle with a 500-, 1500-, and 3000-μm radius) divided in a total of 9 subfields corresponding to 11.1 Macular Photocoagulation Study DA (1 DA equivalent to 2.54 mm 2 of the retina). The grid consisted of white lines and was overlaid on the image electronically ( Supplemental Figure 2 , available at AJO.com ).


Grading of Optical Coherence Tomography Angiography


All OCTA images were acquired with the RTVue XR Avanti (Optovue Inc, Fremont, California, USA) in a manner previously described by Spaide and associates. The instrument captured 2 consecutive B-scans at a fixed location (each containing 304 A-scans at a rate of 70 000 scans per second) before proceeding to another location. Approximately 3 seconds are required to acquire a 3-dimensional vascular cube.


All OCTA scans were reviewed, but only the best-quality 3 × 3-mm and 8 × 8-mm scans centered on the macula and the best 4.5 × 4.5-mm scan centered on the disc (when available) were selected for analysis. Grading was done on the full-thickness 3-dimensional image composed of the superficial, deep, and outer retina vascular layers superimposed. Images were graded using the same protocol described for FA. When there were doubts about the nature of a lesion (for example, for NVE) the OCT co-registered B-scans were evaluated. For the 3 × 3-mm scans only the foveal central subfield and the middle ring (1500 μm radius) were used. For each of the grading features, the superficial capillary plexus (automatically segmented and representing a projection of the vasculature between the retinal nerve fiber layer and the ganglion cell layer) and the deep capillary plexus (automatically segmented and representing the vasculature from the border of the inner plexiform layer and the inner nuclear layer to the border of the inner nuclear layer and the outer plexiform layer) were compared to the full-thickness scan and it was determined if their presence, grade, or total area was different between the 2 layers ( Supplemental Figure 3 , available at AJO.com ). In cases of possible automated software segmentation error, manual adjustment of the boundaries was not performed. The disc scan was graded for presence of ischemia (in the peripapillary retina quadrants) and for the presence of collaterals, NVE, and NVD ( Supplemental Figure 3 ). The grader (J.N.C.) was masked (ie, fundus photographs, FAs, and OCTA images were graded independently). In cases of doubts in the grading, a senior grader (P.A.K.) evaluated the images and any disagreements were resolved by open adjudication. After grading and classification of the images, FA and OCTA 8 × 8-mm and disc scans were compared to evaluate what additional features could be seen in either scan.


Statistical Analysis


Descriptive statistics (percentages, means, and standard deviation) were computed for demographic and clinical variables. Fundus photographs, FA, and OCTA features were categorized and are expressed as percentages. Agreement between the continuous variables graded on FA and OCTA was tested with the intraclass correlation coefficient and are presented as intraclass correlation coefficient (ICC) and 95% confidence intervals (95% CI). Cohen’s unweighted and weighted kappa coefficients were calculated for nominal and ordinal categorical variables, respectively. Logistic regression models were used to test the best-corrected visual acuity (BCVA) low threshold for poor quality of OCTA scans. To compare means, the Mann-Whitney U test was used and to compare categorical variables, the Pearson χ 2 . For all tests, a P < .05 was considered significant. Statistical analyses were performed using SPSS software version 21 (SPSS, Inc, Chicago, Illinois, USA) and MedCalc version 15.8 (Medcalc Software, Ostend, Belgium).




Results


A total of 76 patients (81 eyes) with a history of RVO and OCTA imaging with the RTVue XR Avanti were included in this retrospective analysis. Sixty-nine percent of eyes (n = 56) were imaged 4 or more months after the occlusive episode and 44.4% (n = 36) were of the ischemic type. Patient characteristics are summarized in Table 1 .



Table 1

Baseline Characteristics of 76 Patients With Retinal Vein Occlusion That Were Imaged With Optical Coherence Tomography Angiography (N = 81 Eyes)























































































Age (y), mean ± SD (range) 64.5 ± 14.0 (23–91)
Sex, no. (%) female patients 32 (42.1%)
Eye involvement, no. (%) patients
OD 30 (39.5%)
OS 41 (53.9%)
OU 5 (6.6%)
Type, no. (%) eyes
CRVO 40 (49.4%)
BRVO 34 (42.0%)
HRVO 7 (8.6%)
Quadrant affected (BRVO and HRVO eyes)
Superotemporal, no. (%) 27 (65.9%)
Ischemic type, no. (%) eyes 36 (44.4%)
Time from occlusion, no. (%) eyes
≤1 month 16 (19.8%)
2–3 months 9 (11.1%)
4–6 months 10 (12.3%)
7–12 months 8 (9.9%)
13–24 months 13 (16%)
≥ 25 months 25 (30.9%)
Mean ± SD (range), in months 26.3 ± 36.3 (0.5–180)
BCVA (logMAR), mean ± SD (range)
≥1.30 logMAR, no. (%) eyes
0.71 ± 0.77 (−0.08 to 5.00)
17 (21.0%)
RAPD, no. (%) eyes 4 (4.9%)
Rubeosis iridis, no. (%) eyes 5 (6.2%)
Neovascular glaucoma, no. (%) eyes 2 (2.5%)
Other retinopathies, no. (%) eyes 12 (14.8%)
Previous laser, no. (%) eyes 28 (34.6%)
Previous intravitreal injections, no. (%) eyes
Number of injections, mean ± SD (range)
30 (37.0%)
4.4 ± 4.0 (1–19)

BCVA = best-corrected visual acuity; BRVO = branch retinal vein occlusion; CRVO = central retinal vein occlusion; LogMAR = logarithm of the minimal angle of resolution; OD = right eye; OS = left eye; OU = both eyes; RAPD = relative afferent pupillary defect; SD = standard deviation.


Disease Features on Color Fundus Photography and Fluorescein Angiography


Color fundus photographs (centered on the posterior pole) were available for all of the patients included in the study. In 64 eyes (79.0%) the color photograph was obtained on the same day as OCTA and within 4 weeks in 10 eyes (12.3%). The remaining 7 eyes were excluded from this analysis. IRH were present in half of the study eyes (50.0%) and, in 16.7% of gradable images, total size of IRH was larger than 1 DA. A summary of RVO features graded using color fundus photography is presented in Supplemental Table 1 (Supplemental Material available at AJO.com ).


FA was available for 58 eyes (71.6%) and 29 (50.0%) met the inclusion criteria. From the 29 FAs encompassed in our analysis, 23 (79.3%) were done on the same day as OCTA and 6 (20.7%) were done within 4 weeks, 3 of the 29 FAs had an anti-VEGF intravitreal injection between the 2 scans (10.3%). The majority of the patients were seen in the acute phase (≤3 months) and most features could be graded with confidence, independently of the machine used for the fluorescein angiogram. A summary of the FA results can be seen in Supplemental Table 2 (Supplemental Material available at AJO.com ).


Disease Features on Optical Coherence Tomography Angiography


OCT angiography was acquired in all study eyes (N = 81). However, scanning area and number of scans varied: 79 out of 81 (97.5%) had a 3 × 3-mm scan centered on the macula, 71 (87.7%) had an 8 × 8-mm scan centered on the macula, and 49 (60.5%) had a 4.5 × 4.5-mm scan centered on the disc. Forty-six out of 81 eyes (56.8%) had all 3 scans. Most patients had the OCT angiogram in the chronic phase of the disease. When quality of the scan was adequate or fair, grading could be done with confidence for most features, except for the FAZ radius. In grading the disc scan, confidence for presence of NVD and NVE was high, but it was low for collaterals, as their presence could be affirmed with confidence in 26.1% of cases when they were suspected. When we compared some graded features between the superficial and deep vascular layers, we estimated that differences between the 2 layers were lowest for the presence of collaterals (in the 8 × 8-mm scan) and highest for FAZ radius and area of capillary changes (when graded in the 3 × 3-mm scan). ME was frequently associated with differences in the graded features between the 2 vascular layers, particularly for capillary nonperfusion (χ 2 = 13.54; P < .001). Features graded on OCTA can be seen in Table 2 for the 3 × 3-mm and for the 8 × 8-mm scans and in Table 3 for the 4.5 × 4.5-mm scans centered on the disc. An example of images with grading grids can be seen in Figure 1 .



Table 2

Optical Coherence Tomography Angiography Findings in 3 × 3-mm Scans (N = 79 Eyes) and 8 × 8-mm Scans (N = 71 Eyes) Centered on the Macula, in Eyes With Retinal Vein Occlusion

























































































































































































































































































































































































































3 × 3-mm Scan 8 × 8-mm Scan
CRVO (N = 39) BRVO/HRVO (N = 40) CRVO (N = 36) BRVO/HRVO (N = 35)
Time from occlusion, no. (%)
≤3 months 16 (41.0%) 9 (22.5%) 16 (44.4%) 8 (22.9%)
>3 months 23 (59.0%) 31 (77.5%) 20 (55.6%) 27 (77.1%)
Image quality, no. (%)
Adequate 17 (43.6%) 25 (62.5%) 23 (63.9%) 24 (68.6%)
Fair 12 (30.8%) 9 (22.5%) 8 (22.2%) 7 (20.0%)
Poor/nongradable 10 (25.6%) 6 (15.0%) 5 (13.9%) 4 (11.4%)
Signal strength, mean ± SD (range) 49.4 ± 15.3 (1 – 67) 54.4 ± 13.0 (1 – 83) 44.1 ± 10.9 (13 – 58) 44.3 ± 11.3 (1 – 63)
Causes of poor quality, no. (%)
Opacities 11 (28.2%) 12 (30.0%) 11 (30.6%) 14 (40%)
Motion artifacts 26 (66.7%) 23 (57.5%) 14 (38.9%) 11 (31.4%)
Centering 1 (2.6%) 5 (12.5%) 4 (11.1%) 5 (14.3%)
Segmentation 11 (28.2%) 6 (15.0%) 6 (16.7%) 8 (22.9%)
Area of capillary nonperfusion in inner ETDRS grid (for 3 × 3-mm), no. (%)
0 DA 11 (28.2%) 11 (27.5%)
0.1–0.5 DA 13 (33.3%) 12 (30.0%)
>0.5 DA 5 (12.8%) 11 (27.5%)
Nongradable 10 (25.7%) 6 (15.0%)
DSD 11 (37.9%) 17 (50%)
Area of capillary nonperfusion in ETDRS grid (8 × 8-mm), no. (%)
0 DA 6 (16.7%) 5 (14.3%)
0.1–1 DA 20 (55.5%) 10 (28.6%)
1.1–5 DA (for BRVO/HRVO) 16 (45.7%)
>5 DA (for BRVO/HRVO) 0 (0.0%)
1.1–10 DA (for CRVO) 5 (13.9%)
>10 DA (for CRVO) 0 (0.0%)
Nongradable 5 (13.9%) 4 (11.4%)
DSD 5 (16.1%) 9 (29.0%)
Area of capillary changes in inner ETDRS grid (3 × 3-mm), no. (%)
0 DA 7 (17.9%) 7 (17.5%)
0.1–0.5 DA 15 (38.5%) 18 (45.0%)
>0,5 DA 7 (17.9%) 9 (22.5%)
Nongradable 10 (25.7%) 6 (15.0%)
DSD 24 (85.7%) 30 (90.0%)
Area of capillary changes in ETDRS grid (8 × 8-mm), no. (%)
0 DA 9 (25.0%) 7 (20.0%)
0.1–1.0 DA 16 (44.4%) 9 (25.7%)
>1.0 DA 5 (13.9%) 15 (42.9%)
Nongradable 6 (16.7%) 4 (11.4%)
DSD 10 (33.3%) 14 (45.2%)
Foveal avascular zone radius, no. (%)
<300 μm 2 (5.1%) 3 (7.5%) 2 (5.6%) 4 (11.4%)
300 μm 3 (7.7%) 7 (17.5%) 3 (8.3%) 3 (8.6%)
301–500 μm 18 (46.2%) 21 (52.5%) 22 (61.1%) 21 (60.0%)
>500 μm 0 (0.0%) 2 (5.0%) 0 (0.0%) 1 (2.9%)
Nongradable 16 (41.0%) 7 (17.5%) 9 (25.0%) 6 (17.1%)
DSD 19 (65.5%) 18 (52.9%) 13 (41.9%) 15 (48.4%)
Foveal avascular zone outline, no. (%)
Normal 15 (38.5%) 17 (42.5%) 21 (58.3%) 18 (51.4%)
Questionable 8 (20.5%) 6 (15.0%) 6 (16.7%) 6 (17.1%)
Destroyed <1/2 of circumference 2 (5.1%) 9 (22.5%) 2 (5.6%) 6 (17.1%)
Destroyed >1/2 of circumference, but with remnants 2 (5.1%) 1 (2.5%) 1 (2.8%) 0 (0.0%)
Completely destroyed 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%)
Nongradable 12 (30.8%) 7 (17.5%) 6 (16.7%) 5 (14.3%)
DSD 13 (44.8%) 13 (38.2%) 7 (22.6%) 0 (0.0%)
Collaterals, no. (%)
No 26 (65.0%) 13 (37.1%)
Yes 3 (7.5%) 8 (22.9%)
Questionable 5 (12.5%) 10 (28.6%)
Nongradable 6 (15.0%) 4 (11.4%)
DSD 2 (5.9%) 0 (0.0%)
Neovascularization elsewhere, no. (%)
No 27 (69.2%) 33 (82.5%) 29 (80.5%) 25 (71.4%)
Yes 1 (2.6%) 0 (0.0%) 1 (2.8%) 1 (2.9%)
Questionable 0 (0.0%) 1 (2.5%) 1 (2.8%) 5 (14.3%)
Nongradable 11 (28.2%) 6 (15.0%) 5 (13.9%) 4 (11.4%)

BRVO = branch retinal vein occlusion; CRVO = central retinal vein occlusion; DA = disc areas; DSD = differences between deep and superficial vascular layers (in gradable images); ETDRS = Early Treatment Diabetic Retinopathy Study; HRVO = hemicentral retinal vein occlusion; SD = standard deviation.


Table 3

Optical Coherence Tomography Angiography Findings in 4.5 × 4.5-mm Scans Centered on the Disc (N = 49 Eyes) in Retinal Vein Occlusion Patients




















































































































































CRVO (N = 26) BRVO/HRVO (N = 23)
Time from occlusion, no. (%)
≤3 months 11 (42.3%) 6 (26.1%)
>3 months 15 (57.7%) 17 (73.9%)
Image quality, no. (%)
Adequate 21 (80.8%) 19 (82.6%)
Fair 2 (7.7%) 2 (8.7%)
Poor/nongradable 3 (11.5%) 2 (8.7%)
Signal strength, mean ± SD (range) 49.2 ± 11.8 (12–65) 49.1 ± 18.0 (1–68)
Causes of poor quality, no. (%)
Opacities 5 (19.2%) 6 (26.1%)
Motion artifacts 7 (26.9%) 6 (26.1%)
Centering 2 (7.7%) 1 (4.3%)
Segmentation 9 (34.6%) 2 (8.7%)
Number of peripapillary retinal quadrants with ischemia, no. (%)
0 16 (61.5%) 11 (47.8%)
1 2 (7.7%) 4 (17.4%)
2 3 (11.5%) 6 (26.1%)
3 1 (3.8%) 0 (0.0%)
4 1 (3.8%) 0 (0.0%)
Nongradable 3 (11.5%) 2 (8.7%)
Collaterals, no. (%)
No 7 (26.9%) 14 (60.9%)
Yes 4 (15.4%) 2 (8.7%)
Questionable 12 (46.2%) 5 (21.7%)
Nongradable 3 (11.5%) 2 (8.7%)
Neovascularization of disc, no. (%)
No 21 (91.3%) 18 (78.3%)
Yes 2 (8.7%) 2 (8.7%)
Questionable 0 (0.0%) 1 (4.3%)
Nongradable 3 (11.5%) 2 (8.7%)
Neovascularization elsewhere, no. (%)
No 23 (100.0%) 20 (87.0%)
Yes 0 (0.0%) 1 (4.3%)
Questionable 0 (0.0%) 0 (0.0%)
Nongradable 3 (11.5%) 2 (8.7%)

BRVO = branch retinal vein occlusion; CRVO = central retinal vein occlusion; HRVO = hemicentral retinal vein occlusion; SD = standard deviation.



Figure 1


Multimodal analysis with optical coherence tomography (OCT) angiography, color fundus photography, and fluorescein angiography of a 65-year-old woman with a branch retinal vein occlusion of the right eye, exemplifying good correspondence between these imaging techniques. (Top) The upper image corresponds to a montage with OCT angiography images (8 × 8-mm centered on the macula, 6 × 6-mm of the periphery, and 4.5 × 4.5-mm disc scans). (Middle) Images correspond to the OCT angiography 3 × 3-mm macular scan (left), the 8 × 8-mm macular scan (center left), and the 4.5 × 4.5-mm disc scan (center) used for grading. The preretinal nature of the disc neovascularization on the disc OCT angiography scan (center) could be identified in the superotemporal quadrant if the automatically segmented vitreous scan (center right) or the co-registered B-scans (right) were analyzed. (Bottom) Row corresponds to the color fundus photograph (left) and mid-phase (center) and late-phase fluorescein angiography (right) used for grading.


Assessment of Image Quality and Artifacts


When compared to the other imaging modalities, quality of scans was a major issue in OCTA. For fundus photographs, images were classified as adequate for grading in 78.4%, fair in 18.9% and nongradable in 2.7% vs 54.2%, 27.8%, and 18.0% for 3 × 3-mm scans and 66.1%, 23.1%, and 10.8% for 8 × 8-mm scans, respectively. In FA, images were adequate for grading in 82.8%, fair in 13.8%, and nongradable in 3.4% vs 41.4%, 31.0%, and 27.6% for the corresponding 3 × 3-mm scans and 46.2%, 38.5%, and 15.4% for the 8 × 8-mm scans, respectively. The main causes for quality problems in OCTA were motion artifacts (particularly for the 3 × 3-mm) and opacities in ocular media. However, even if 16 out of the 79 3 × 3-mm scans had insufficient quality for grading (20.3%), presence or absence of ischemia could be evaluated in 6 of the 16 scans (37.5%). In the 8 × 8-mm scans, 9 out of 71 (12.7%) had insufficient quality for grading, but ischemia could be evaluated in 5 of these scans (55.6%) ( Figure 2 ). Presence of ischemia, NVD, and NVE could also be inferred in the only nongradable FA. The main variable associated with poor quality of OCTA was worst BCVA (odds ratio = 27.5 [95% CI 5.8–130.1; P < .001] for the 3 × 3-mm and odds ratio = 12.1 [95% CI 2.9–50.3; P < .01], using BCVA as a continuous variable). Factors associated with worst BCVA were also associated with worst-quality scans (ischemic type, previous laser, relative afferent pupillary defect [RAPD], and rubeosis iridis, but not ME or previous injections [data not presented]). We also tested different BCVA cutoffs for worst-quality OCTA 3 × 3-mm scans (0.7, 1.0, 1.3, and 2.0 logarithm of the minimal angle of resolution [logMAR]) and found BCVA worse than 1.3 logMAR as the better predictor for nongradable images (odds ratio = 44.25 [95% CI 9.7–202.1; P < .001]).




Figure 2


A 49-year-old patient with central retinal vein occlusion, macular ischemia, and hand movement visual acuity. Owing to motion artifacts, a low signal, and segmentation errors, the optical coherence tomography angiography 8 × 8-mm scan was considered nongradable (Right). However, the ischemic nature of the central retinal vein occlusion could be correctly assessed and was confirmed by fluorescein angiography (Center). A color fundus photograph is added for comparison (Left).


Agreement Between Fluorescein Angiography and Optical Coherence Tomography Angiography Features of Retinal Vein Occlusion


Agreement between FA and OCTA was tested when both examinations were available and gradable ( Table 4 ). Twenty-one eyes had a gradable 3 × 3-mm and 21 a gradable 8 × 8-mm scan. One eye was excluded from both analyses owing to insufficient quality of FA and OCTA. There was good agreement between both imaging techniques for area of ischemia (ICC 0.825 [95% CI 0.616–0.925] for the 3 × 3-mm and 0.891 [95% CI 0.752–0.954] for the 8 × 8-mm), values that increased when OCTA image quality was adequate. Agreement between area of capillary changes was still significant, but poorer. Figure 3 shows the agreement for capillary nonperfusion and capillary changes by Bland-Altman plot. For the FAZ grading, agreement was good for evaluated parameters between the FA and the 3 × 3-mm scan, but poor between the FA and the 8 × 8-mm scan. For the presence of collateral vessels (in BRVO/HRVO) agreement was poor between FA and OCTA. In NVE, agreement was substantial between the FA and the 8 × 8-mm scan ( Figure 1 ). Seventeen patients had both an FA and an OCTA of the disc. Agreement between NVD in the 2 imaging techniques was good (15 out of 17 eyes [88.2%] were graded the same way), but because only 1 eye had definite neovascularization, kappa value was 0.433 (95% CI 0–1.000).



Table 4

Agreement Between Graded Features on Fluorescein Angiography and Optical Coherence Tomography Angiography (3 × 3-mm Scans [N = 21 Eyes] and 8 × 8-mm Scans [N = 21 Eyes] Centered on the Macula) in Retinal Vein Occlusion Patients















































































































































































































































































































































































3 × 3-mm Scan 8 × 8-mm Scan
FA OCTA Coefficient 95% CI FA OCTA Coefficient 95% CI
Area of ischemia (DA), mean ± SD
All examinations 0.32 ± 0.37 a 0.33 ± 0.38 a 0.825 b 0.616–0.925 1.55 ± 2.16 a 1.44 ± 1.66 a 0.891 b 0.752–0.954
Only OCTA 3 × 3-mm adequate quality 0.33 ± 0.36 a 0.34 ± 0.42 a 0.896 b 0.676–0.969 1.29 ± 1.86 a 1.30 ± 1.70 a 0.985 b 0.973–0.998
Area of capillary changes (DA), mean ± SD
All examinations 0.24 ± 0.27 a 0.34 ± 0.33 a 0.712 b 0.413–0.874 1.22 ± 1.39 a 0.91 ± 1.02 a 0.787 b 0.514–0.910
Only OCTA 3 × 3-mm adequate quality 0.21 ± 0.22 a 0.24 ± 0.29 a 0.812 b 0.494–0.944 1.04 ± 1.44 a 0.93 ± 1.21 a 0.926 b 0.760–0.979
Foveal avascular zone radius (all examinations), no. 1.000 c , d 1.000–1.000 0.156 c , d 0–0.508
<300 μm 1 1 2 1
300 μm 1 1 1 1
300–500 μm 18 17 17 16
>500 μm 0 0 0 1
Cannot grade 1 2 1 2
Foveal avascular zone radius (only adequate quality), no. 1.000 c 1.000–1.000 −0.065 c −0.156 to 0.027
<300 μm 1 1 1 0
300 μm 1 1 0 1
300–500 μm 9 9 10 10
>500 μm 0 0 0 0
Foveal outline (all examinations), no. 0.799 c 0.612–0.986 0.600 c 0.367–0.834
Outline normal 9 11 8 13
Outline questionable 5 3 5 2
Outline destroyed <1/2 7 7 6 6
Outline destroyed <1/2, but with remnants 0 0 2 0
Foveal outline (only adequate quality), no. 0.904 c 0.722–1.000 0.732 c 0.419–1.000
Outline normal 6 7 6 7
Outline questionable 1 0 1 1
Outline destroyed <1/2 4 4 3 3
Outline destroyed <1/2, but with remnants 0 0 1 0
Collaterals (for BRVO/HRVO), no 0.242 c 0–0.554 0.211 c 0–0.619
Absent 3 8 2 4
Present 5 0 5 2
Questionable 2 2 2 3
Neovascularization elsewhere, no. e 0.667 c 0.303–1.000
Absent 16 17
Present 4 2
Questionable 0 1

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Jan 6, 2017 | Posted by in OPHTHALMOLOGY | Comments Off on Systematic Evaluation of Optical Coherence Tomography Angiography in Retinal Vein Occlusion

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