Purpose
To compare visualization of choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) using an ultrahigh-speed swept-source (SS) optical coherence tomography angiography (OCTA) prototype vs a spectral-domain (SD) OCTA device.
Design
Comparative analysis of diagnostic instruments.
Methods
Patients were prospectively recruited to be imaged on SD OCT and SS OCT devices on the same day. The SD OCT device employed is the RTVue Avanti (Optovue, Inc, Fremont, California, USA), which operates at ∼840 nm wavelength and 70 000 A-scans/second. The SS OCT device used is an ultrahigh-speed long-wavelength prototype that operates at ∼1050 nm wavelength and 400 000 A-scans/second. Two observers independently measured the CNV area on OCTA en face images from the 2 devices. The nonparametric Wilcoxon signed rank test was used to compare area measurements and P values of <.05 were considered statistically significant.
Results
Fourteen eyes from 13 patients were enrolled. The CNV in 11 eyes (78.6%) were classified as type 1, 2 eyes (14.3%) as type 2, and 1 eye (7.1%) as mixed type. Total CNV area measured using SS OCT and SD OCT 3 mm × 3 mm OCTA were 0.949 ± 1.168 mm 2 and 0.340 ± 0.301 mm 2 , respectively ( P = .001). For the 6 mm × 6 mm OCTA the total CNV area using SS OCT and SD OCT were 1.218 ± 1.284 mm 2 and 0.604 ± 0.597 mm 2 , respectively ( P = .0019). The field of view did not significantly affect the measured CNV area ( P = .19 and P = .18 for SS OCT and SD OCT, respectively).
Conclusion
SS OCTA yielded significantly larger CNV areas than SD OCTA. It is possible that SS OCTA is better able to demarcate the full extent of CNV vasculature.
Fluorescein angiography (FA) and indocyanine green angiography (ICGA) are considered the gold standard for imaging the retinal and choroidal vasculature and, in particular, for imaging choroidal neovascularization. These imaging modalities are dynamic and visualize dye transit over time, allowing direct visualization of large vessel filling and eventual leakage and/or pooling of dye. However, small retinal vessels and feeder vessels are often obscured by subsequent hyperfluorescence, especially in the late phase of dye transit, and may limit precise assessment of the extent of neovascularization. In addition, these modalities are invasive, involving the use of intravenous contrast that can result in systemic side effects and, rarely, anaphylaxis.
Optical coherence tomography angiography (OCTA) is a noninvasive technology that uses the decorrelation motion contrast between rapidly repeated optical coherence tomography (OCT) B-scans to visualize blood flow. Recently, spectral-domain (SD) OCTA systems were introduced using prototype software on a commercially available device operating at a ∼840 nm wavelength. Using SD OCTA, evaluation of choroidal neovascularization (CNV) in eyes with wet age-related macular degeneration (AMD) has been described. However, since these systems operate at short wavelengths, visualization beneath the retinal pigment epithelium (RPE) may be obscured owing to signal attenuation from the RPE–Bruch membrane complex.
Swept-source optical coherence tomography (SS OCT) technology uses a longer, ∼1050 nm wavelength and has less variation in sensitivity with depth (sensitivity roll-off) compared with SD OCT, allowing improved immunity to ocular opacity and deeper penetration into the choroid. This allows an improved visualization of the choroid both on cross-sectional and en face OCTA imaging, and may also improve visualization of CNV, especially the sub-RPE component of the membrane. As OCTA imaging becomes more ubiquitous, a comparison between these 2 imaging paradigms—SD OCT and SS OCT—becomes increasingly important. The present study aimed to use an ultrahigh-speed SS OCT prototype to analyze the extent of CNV and quantify its area in eyes with wet AMD when compared to SD OCT.
Methods
This was a comparative analysis of diagnostic instruments conducted at the New England Eye Center of Tufts Medical Center (Boston, Massachusetts, USA) and approved by the Tufts Medical Center and Massachusetts Institute of Technology Institutional Review Boards. The research adhered to the tenets of the Declaration of Helsinki and complied with the Health Insurance Portability and Accountability Act of 1996. Written informed consent was obtained before OCTA imaging.
Patient Selection
Patients with CNV secondary to AMD were seen at the retina service of New England Eye Center between August 2014 and May 2015 and prospectively recruited to be imaged on SD OCT and SS OCT. To be included, a comprehensive chart review was performed to confirm the diagnosis of CNV secondary to wet AMD that was made by a retina specialist on the basis of a complete ophthalmic evaluation including dilated fundus examination, standard structural SD OCT imaging, and FA and/or ICGA.
Image Acquisition and Analysis
All patients were imaged on SD OCT and SS OCT on the same day. The SD OCT instrument was the RTVue Avanti with prototype AngioVue software for OCTA (Optovue, Inc, Fremont, California, USA). This instrument operates at ∼840 nm wavelength and 70 000 A-scans per second to acquire OCTA volumes consisting of 2 repeated B-scans from 304 sequentially uniformly spaced locations. Each B-scan consisted of 304 A-scans for a total of 2 × 304 × 304 A-scans per acquisition, with a total acquisition time of approximately 3 seconds, and an axial optical resolution of ∼5 μm. Split-spectrum amplitude-decorrelation angiography (SSADA) was employed to improve the signal-to-noise ratio. Motion correction was performed using registration of 2 orthogonally acquired volumes. The SS OCT device was an ultrahigh-speed ∼1050 nm prototype developed at Massachusetts Institute of Technology (Cambridge, Massachusetts, USA) and deployed to New England Eye Center. It uses a high-speed vertical-cavity surface-emitting laser as the light source and operates at a ∼1050 nm wavelength, achieving a speed of 400 000 A-scans per second, and acquires a total of 5 repeated B-scans from 500 sequentially uniformly spaced locations. Each B-scan consisted of 500 A-scans, and the interscan time was approximately 1.5 ms (accounting for the galvanometer mirror scanning duty cycle). A total of 5 × 500 × 500 A-scans were acquired per OCTA volume with an acquisition time of approximately 3.8 seconds and an axial optical resolution of ∼8–9 μm. For both 3 mm × 3 mm and 6 mm × 6 mm, the acquired OCT volumes were centered on the fovea. There was no eye tracking used for fixation in the SS OCT. The patients were asked to fixate on an internal target during OCTA acquisition. The motion correction algorithm on the SS OCT prototype is similar to the SD OCT system and consists of acquiring OCTA volumes in orthogonal X-fast and Y-fast directions. From these 2 orthogonal scans a single merged volume is constructed that has superior signal quality and reduced motion artifacts.
Two independent and masked readers (E.A.N. and R.N.L.) of the Boston Image Reading Center analyzed the 3 mm × 3 mm and 6 mm × 6 mm OCTA images from both devices to determine the extent of CNV. For the SD OCT images, they used the automatic segmentation of the retinal layers at the level of the choriocapillaris generated by the AngioVue software in an orthogonal view. In order to correct for automated segmentation error and projection artifacts, which can obscure the full extent of the CNV, the segmentation slab was manually adjusted, using corresponding structural OCT B-scans as a guide for the placement of 2 parallel segmentation lines at sequential depths, so as to best visualize the CNV complex. This semi-automatic method allowed the readers to select images that visualized the largest extent of the CNV for subsequent quantitative analysis. For the SS OCT images, a custom C++ application was used for processing, and ImageJ (National Institutes of Health, Bethesda, Maryland, USA) was used for visualization. A flat segmentation line was manually adjusted using the orthogonal view, and en face OCTA images were computed by projecting the OCTA data through the depths spanned by the lesion.
Two observers independently measured the area of CNV on OCTA images from the 2 instruments using ImageJ. Both 3 mm × 3 mm and 6 mm × 6 mm OCTA images were quantitatively analyzed. The pixel dimensions of the original images were used to set the scale using ImageJ plug-ins prior to performing the measurements. The measurements were rescaled to the millimeter square unit using pixel dimensions of the OCTA images.
Data Statistical Analysis
Statistical analysis was performed with Stata 14. Intraclass correlation coefficient (ICC) was used to estimate the agreement between individual measurements from both readers. Since the ICC was consistently >0.9 between the 2 readers, the Wilcoxon signed rank test was used to compare area measurements performed by 1 reader on SD OCT and SS OCT 3 mm × 3 mm and 6 mm × 6 mm OCTA scans. P values of <.05 were considered statistically significant.
Results
Patient Demographics
Fourteen eyes from 13 white patients were enrolled in this study. Nine patients (64.3%) were female and 5 (35.7%) were male. The mean age of the studied population was 73.5 ± 10.6 years. All patients had anti–vascular endothelial growth factor (anti-VEGF) treatment prior to imaging. Patient demographics and number of intravitreous injections are listed in the Table .
| Age | Sex | CNV Type | Number of Anti-VEGF IVI | Time Since Last Anti-VEGF IVI (Weeks) | SS OCT 3 × 3 (mm 2 ) | SD OCT 3 × 3 (mm 2 ) | SS OCT 6 × 6 (mm 2 ) | SD OCT 6 × 6 (mm 2 ) |
|---|---|---|---|---|---|---|---|---|
| 79 | F | 1 | 35 | 9 | 4.624 | 0.536 | Not available | Not available |
| 87 | F | 1 | 3 | 6 | 1.111 | 0.680 | 4.236 | 1.038 |
| 56 | M | 2 | 2 | 8 | 0.787 | 0.519 | 1.492 | 0.519 |
| 61 | F | 1 | 11 | 13 | 0.541 | 0.279 | 0.437 | 0.167 |
| 66 | F | 1 | 1 | 4 | 0.632 | CNV not identified | 0.507 | CNV not identified |
| 81 | M | 1 | 3 | 4 | 0.405 | 0.371 | 0.368 | 0.355 |
| 73 | F | 1 | 17 | 8 | 0.482 | 0.121 | 0.365 | 0.303 |
| 57 | F | Mixed | 2 | 4 | 0.121 | 0.093 | 0.105 | 0.108 |
| 83 | M | 1 | 6 | 12 | 0.634 | 0.271 | 0.489 | 0.418 |
| 83 | M | 2 | 8 | 12 | 0.368 | 0.253 | 1.107 | 0.584 |
| 69 | F | 1 | 4 | 8 | 1.901 | 0.386 | 3.391 | 1.973 |
| 83 | F | 1 | 16 | 10 | 0.229 | 0.039 | 1.611 | 1.586 |
| 68 | F | 1 | 2 | 15 | 0.108 | 0.105 | 0.110 | 0.099 |
| 83 | M | 1 | 13 | 16 | 1.348 | 1.119 | 1.623 | 0.712 |
Qualitative Analysis
OCTA enabled detailed en face visualization of the neovascular complex; the corresponding structural OCT B-scans helped identify the depth and location of the CNV relative to the RPE. Features on B-scan such as the presence or absence of subretinal fluid, intraretinal fluid, subretinal hyperreflective material, and pigment epithelial detachment were evaluated and found to be identical between the SS OCT and the SD OCT images. The CNV for each patient was classified using OCTA and corresponding structural B-scans: type 1 when the CNV complex was under the RPE; type 2 when it was above the RPE; and mixed when both components were present. Of the 14 eyes from 13 patients enrolled in this study, 11 (78.6%) presented a type 1 CNV, 2 (14.3%) presented a type 2 CNV, and only 1 eye (7.1%) had the mixed type. CNV classifications for each patient are listed in the Table . All eyes were imaged with both devices using 3 × 3 mm and 6 × 6 mm protocols. In 1 eye, only 3 × 3 mm images were used, as the 6 × 6 mm images from the SD OCT were of too poor quality for analysis.
In 26 of 27 images analyzed with 3 mm × 3 mm (14) and 6 mm × 6 mm (13) OCTA, SS OCT visualized a larger area of the CNV complex compared to SD OCT. This discrepancy in the extent of CNV visualized by the 2 devices was correlated with corresponding FA images when present. It appeared that the occult part of the CNV was the major contributor to the difference in the extent of CNV visualized by the 2 devices. SD OCT at ∼840 nm wavelength is unable to completely visualize the occult component of the neovascular membrane in all patients ( Figure 1 ). Additionally, in 1 patient with type 1 (occult) CNV, SD OCT was unable to identify the neovascular membrane, whereas SS OCT at ∼1050 nm wavelength was able to clearly capture the full extent of the membrane ( Figure 2 ). Both instruments, however, were able to identify the feeder vessel ( Figure 3 ). Using the 3 mm × 3 mm field of view, both the SD OCT and SS OCT instruments visualized the feeder vessel in 5 of the 14 eyes (35.7%). Using the 6 mm × 6 mm field of view, SD OCT and SS OCT visualized the feeder vessels in 5 of 13 (38.5%) and 6 of 13 eyes (46.2%), respectively ( Figure 4 ).
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