The clinical evaluation of a widefield lens to expand the field of view in optical coherence tomography (OCT-A).

This study aimed to evaluate the clinical benefits of incorporating a widefield lens (WFL) in optical coherence tomography angiography (OCT-A) in patients with retinal vascular diseases in comparison to standard single-shot OCT-A scans. Sixty patients with retinal vascular diseases including diabetic retinopathy (DR) and retinal vein occlusion (RVO) were recruited. OCT-A imaging (PlexElite 9000) with and without WFL was performed in randomized order. The assessment included patient comfort, time, field of view (FoV), image quality and pathology detection. Statistical analysis included paired t-tests, Mann-Whitney U-tests and Bonferroni correction for multiple tests, with inter-grader agreement using the kappa coefficient. Using a WFL did not lead to statistically significant differences in DR and RVO group test times. Patient comfort remained high, with similar responses for WFL and non-WFL measurements. The WFL notably expanded the scan field (1.6× FoV increase), enhancing peripheral retinal visibility. However, image quality varied due to pathology and eye dominance, affecting the detection of peripheral issues in RVO and DR cases. The use of a WFL widens the scan field, aiding vascular retinal disease imaging with minor effects on comfort, time, and image quality. Further enhancements are needed for broader view angles, enabling improved quantification of non-perfused areas and more reliable peripheral proliferation detection.

Pseudoaveraging for denoising of OCT angiography: a deep learning approach for image quality enhancement in healthy and diabetic eyes.

BACKGROUND: This study aimed to develop a deep learning (DL) algorithm that enhances the quality of a single-frame enface OCTA scan to make it comparable to 4-frame averaged scan without the need for the repeated acquisitions required for averaging. METHODS: Each of the healthy eyes and eyes from diabetic subjects that were prospectively enrolled in this cross-sectional study underwent four repeated 6 × 6 mm macular scans (PLEX Elite 9000 SS-OCT), and the repeated scans of each eye were co-registered to produce 4-frame averages. This prospective dataset of original (single-frame) enface scans and their corresponding averaged scans was divided into a training dataset and a validation dataset. In the training dataset, a DL algorithm (named pseudoaveraging) was trained using original scans as input and 4-frame averages as target. In the validation dataset, the pseudoaveraging algorithm was applied to single-frame scans to produce pseudoaveraged scans, and the single-frame and its corresponding averaged and pseudoaveraged scans were all qualitatively compared. In a separate retrospectively collected dataset of single-frame scans from eyes of diabetic subjects, the DL algorithm was applied, and the produced pseudoaveraged scan was qualitatively compared against its corresponding original. RESULTS: This study included 39 eyes that comprised the prospective dataset (split into 5 eyes for training and 34 eyes for validating the DL algorithm), and 105 eyes that comprised the retrospective test dataset. Of the total 144 study eyes, 58% had any level of diabetic retinopathy (with and without diabetic macular edema), and the rest were from healthy eyes or eyes of diabetic subjects but without diabetic retinopathy and without macular edema. Grading results in the validation dataset showed that the pseudoaveraged enface scan ranked best in overall scan quality, background noise reduction, and visibility of microaneurysms (p < 0.05). Averaged scan ranked best for motion artifact reduction (p < 0.05). Grading results in the test dataset showed that pseudoaveraging resulted in enhanced small vessels, reduction of background noise, and motion artifact in 100%, 82%, and 98% of scans, respectively. Rates of false-positive/-negative perfusion were zero. CONCLUSION: Pseudoaveraging is a feasible DL approach to more efficiently improve enface OCTA scan quality without introducing notable image artifacts.

Retinal capillary and choriocapillaris assessment using a beam modifier optical coherence tomography angiography module to increase lateral optical resolution.

PURPOSE: To assess a new optical coherence tomography angiography (OCTA) technology and its contribution to retinal vascularization and choriocapillaris (CC) exploration. METHODS: A new module, named "Beam expander" (BE), which increases the lateral resolution of OCTA, was used in combination with a prototype software in the PLEX® Elite 9000 Swept-Source OCT instrument (ZEISS, Dublin, CA). This prospective study involved 22 healthy subjects imaged with and without BE. Qualitative analysis of superficial capillary plexus (SCP), deep capillary complex (DCC) retinal and CC angiograms were performed. Perfusion density (PD), vessel density (VD), and foveal avascular zone (FAZ) measurements were also compared. RESULTS: Qualitative analysis of single SCP and DCC retinal angiograms acquired with BE showed significantly better vessel sharpness (respectively, p = 0.0002, and p<0.0001), and greater peripheral image quality (p = 0.028 and p = 0.007) compared to standard OCTA images. Mean VD of whole retina single scans was significantly higher for BE angiograms compared to classic angiograms (28.16 ±1.29 mm-1 and 23.36 ±0.92 mm-1, respectively, p<0.0001). Repeatability of VD, PD and FAZ raw size were found to be similar between the two methods (intraclass correlation coefficient: 0.671, 0.604 and 0.994 with BE versus 0.764, 0.638 and 0.990 without BE). CC image quality was found to be significantly superior with BE, and flow deficits were more visible in all BE scans compared to standard scans. CONCLUSIONS: An increase in lateral resolution of the OCT beam resulted in higher quality of retinal and choriocapillaris OCTA images in healthy subjects. These results provide significant insights into the future OCTA imaging enhancements.

Swept-source OCTA quantification of capillary closure predicts ETDRS severity staging of NPDR.

PURPOSE: To test whether a single or composite set of parameters evaluated with optical coherence tomography angiography (OCTA), representing retinal capillary closure, can predict non-proliferative diabetic retinopathy (NPDR) staging according to the gold standard ETDRS grading scheme. METHODS: 105 patients with diabetes, either without retinopathy or with different degrees of retinopathy (NPDR up to ETDRS grade 53), were prospectively evaluated using swept-source OCTA (SS-OCTA, PlexElite, Carl Zeiss Meditec) with 15×9 mm and 3×3 mm angiography protocols. Seven-field photographs of the fundus were obtained for ETDRS staging. Eyes from age-matched healthy subjects were also imaged as control. RESULTS: In eyes of patients with type 2 diabetes without retinopathy or ETDRS levels 20 and 35, retinal capillary closure was in the macular area, with predominant alterations in the parafoveal retinal circulation (inner ring). Retinal capillary closure in ETDRS stages 43-53 becomes predominant in the retinal midperiphery with vessel density average values of 25.2±7.9 (p=0.001) in ETDRS 43 and 23.5±3.4 (p=0.001) in ETDRS 47-53, when evaluating extended areas of 15×9 protocol. Combination of acquisition protocols 3×3 mm and 15×9 mm, using SS-OCTA, allows discrimination between eyes with mild NPDR (ETDRS 10, 20, 35) and eyes with moderate-to-severe NPDR (ETDRS grades 43-53). CONCLUSIONS: Retinal capillary closure, quantified by SS-OCTA, can identify NPDR severity progression. It is located mainly in the perifoveal retinal capillary circulation in the initial stages of NPDR, whereas the retinal midperiphery is predominantly affected in moderate-to-severe NPDR.

Optical Coherence Tomography Angiography Metrics Monitor Severity Progression of Diabetic Retinopathy-3-Year Longitudinal Study.

To examine retinal vessel closure metrics and neurodegenerative changes occurring in the initial stages of nonproliferative diabetic retinopathy (NPDR) and severity progression in a three-year period. Methods: Three-year prospective longitudinal observational cohort of individuals with type 2 diabetes (T2D), one eye per person, using spectral domain-optical coherence tomography (SD-OCT) and OCT-Angiography (OCTA). Eyes were examined four times with one-year intervals. OCTA vessel density maps of the retina were used to quantify vessel closure. Thickness of the ganglion cell + inner plexiform layer (GCL + IPL) was examined to identify retinal neurodegenerative changes. Diabetic retinopathy ETDRS classification was performed using the seven-field ETDRS protocol. Results: A total of 78 eyes/patients, aged 52 to 80 years, with T2D and ETDRS grades from 10 to 47 were followed for 3 years with annual examinations. A progressive increase in retinal vessel closure was observed. Vessel density (VD) showed higher decreases with retinopathy worsening demonstrated by step-changes in ETDRS severity scale (p < 0.001). No clear correlation was observed between neurodegenerative changes and retinopathy progression. Conclusions: Retinal vessel closure in NPDR correlates with DR severity progression. Our findings provide supporting evidence that OCTA metrics of vessel closure may be used as a surrogate for DR severity progression.

Natural History of Subclinical Neovascularization in Nonexudative Age-Related Macular Degeneration Using Swept-Source OCT Angiography.

PURPOSE: Swept-source (SS) OCT angiography (OCTA) was used to determine the prevalence, incidence, and natural history of subclinical macular neovascularization (MNV) in eyes with nonexudative age-related macular degeneration (AMD). DESIGN: Prospective, observational, consecutive case series. PARTICIPANTS: Patients with intermediate AMD (iAMD) or geographic atrophy (GA) secondary to nonexudative AMD in 1 eye and exudative AMD in the fellow eye. METHODS: All patients were imaged using both the 3×3 mm and 6×6 mm SS OCTA fields of view (PLEX Elite 9000; Carl Zeiss Meditec, Inc, Dublin, CA). The en face slab used to detect the MNV extended from the outer retina to the choriocapillaris, and projection artifacts were removed using a proprietary algorithm. MAIN OUTCOME MEASURES: Prevalence of subclinical MNV and time to exudation with Kaplan-Meier cumulative estimates of exudation at 1 year. RESULTS: From August 2014 through March 2017, 160 patients underwent SS OCTA (110 eyes with iAMD and 50 eyes with GA). Swept-source OCTA identified subclinical MNV at the time of first imaging in 23 of 160 eyes, for a prevalence of 14.4%. Six eyes demonstrated subclinical MNV during the follow-up. Of 134 eyes with follow-up visits, a total of 13 eyes demonstrated exudation, and of these 13 eyes, 10 eyes were found to have pre-existing subclinical MNV. By 12 months, the Kaplan-Meier cumulative incidence of exudation for all 134 eyes was 6.8%. For eyes with subclinical MNV at the time of first SS OCTA imaging, the incidence was 21.1%, and for eyes without subclinical MNV, the incidence was 3.6%. There was no difference in the cumulative incidence of exudation from pre-existing MNV in eyes with iAMD or GA (P = 0.847, log-rank test). After the detection of subclinical MNV, the risk of exudation was 15.2 times (95% confidence interval, 4.2-55.4) greater compared with eyes without subclinical MNV. CONCLUSIONS: By 12 months, the risk of exudation was greater for eyes with documented subclinical MNV compared with eyes without detectable MNV. For eyes with subclinical MNV, recommendations include more frequent follow-up and home monitoring. Intravitreal therapy is not recommended until prospective studies are performed.

Comparison of Neovascular Lesion Area Measurements From Different Swept-Source OCT Angiographic Scan Patterns in Age-Related Macular Degeneration.

Purpose: We compared area measurements for the same neovascular lesions imaged using swept source optical coherence tomography angiography (SS-OCTA) and enlarging scan patterns. Methods: Patients with neovascular age-related macular degeneration were imaged using a 100-kHz SS-OCTA instrument (PLEX Elite 9000). The scanning protocols included the 3 × 3, 6 × 6, 9 × 9, and 12 × 12 mm fields of view. Two groups were studied. Group 1 included small lesions contained within the 3 \( \times \) 3 mm scan, and Group 2 included larger lesions that were fully contained within the 6 \( \times \) 6 mm scan. Results: A total of 30 eyes of 26 patients were enrolled in Group 1 and 30 eyes of 25 patients were enrolled in Group 2. In Group 1, the automated mean lesion area measurements were 1.11 (SD = 0.78), 1.14 (SD = 0.80), and 1.27 (SD = 0.82) mm2 for the 3 \( \times \) 3, 6 \( \times \) 6, and 12 \( \times \) 12 mm scans, respectively (ANOVA P < 0.001; post hoc comparisons, P = 0.184, 3 \( \times \) 3 vs. 6 \( \times \) 6 mm; P < 0.001 for the other two pairs). In Group 2, the automated mean lesion area measurements were 5.43 (SD = 2.56), 5.53 (SD = 2.48), and 5.49 (SD = 2.65) mm2 for the 6 \( \times \) 6, 9 \( \times \) 9, and 12 \( \times \) 12 mm scans, respectively (ANOVA P = 0.435; post-hoc comparisons, P = 0.062, 6 \( \times \) 6 vs. 9 \( \times \) 9 mm; P = 0.553, 6 \( \times \) 6 vs. 12 \( \times \) 12 mm; P = 0.654, 9 \( \times \) 9 vs. 12 \( \times \) 12 mm). Conclusions: The similarity in lesion area measurements across different scan patterns suggests that SS-OCTA imaging can be used to follow quantitatively the enlargement of choroidal neovascularization as the disease progresses.

Comparison Between Spectral-Domain and Swept-Source Optical Coherence Tomography Angiographic Imaging of Choroidal Neovascularization.

Purpose: The purpose of this study was to compare imaging of choroidal neovascularization (CNV) using swept-source (SS) and spectral-domain (SD) optical coherence tomography angiography (OCTA). Methods: Optical coherence tomography angiography was performed using a 100-kHz SS-OCT instrument and a 68-kHz SD-OCTA instrument (Carl Zeiss Meditec, Inc.). Both 3 × 3- and 6 × 6-mm2 scans were obtained on both instruments. The 3 × 3-mm2 SS-OCTA scans consisted of 300 A-scans per B-scan at 300 B-scan positions, and the SD-OCTA scans consisted of 245 A-scans at 245 B-scan positions. The 6 × 6-mm2 SS-OCTA scans consisted of 420 A-scans per B-scan at 420 B-scan positions, and the SD-OCTA scans consisted of 350 A-scans and 350 B-scan positions. B-scans were repeated four times at each position in the 3 × 3-mm2 scans and twice in the 6 × 6-mm2 scans. Choroidal neovascularization was excluded if not fully contained within the 3 × 3-mm2 scans. The same algorithm was used to detect CNV on both instruments. Two graders outlined the CNV, and the lesion areas were compared between instruments. Results: Twenty-seven consecutive eyes from 23 patients were analyzed. For the 3 × 3-mm2 scans, the mean lesion areas for the SS-OCTA and SD-OCTA instruments were 1.17 and 1.01 mm2, respectively (P = 0.047). For the 6 × 6-mm2 scans, the mean lesion areas for the SS-OCTA and SD-OCTA instruments were 1.24 and 0.74 mm2 (P = 0.003). Conclusions: The areas of CNV tended to be larger when imaged with SS-OCTA than with SD-OCTA, and this difference was greater for the 6 × 6-mm2 scans.

Automated Quantitation of Choroidal Neovascularization: A Comparison Study Between Spectral-Domain and Swept-Source OCT Angiograms.

Purpose: To compare the lesion sizes of choroidal neovascularization (CNV) imaged with spectral-domain (SD) and swept-source (SS) optical coherence tomography angiography (OCTA) and measured using an automated detection algorithm. Methods: Patients diagnosed with CNV were imaged by SD-OCTA and SS-OCTA systems using 3 × 3-mm and 6 × 6-mm scans. The complex optical microangiography (OMAGC) algorithm was used to generate the OCTA images. Optical coherence tomography A datasets for imaging CNV were derived by segmenting from the outer retina to 8 µm below Bruch's membrane. An artifact removal algorithm was used to generate angiograms free of retinal vessel projection artifacts. An automated detection algorithm was developed to quantify the size of the CNV. Automated measurements were compared with manual measurements. Measurements from SD-OCTA and SS-OCTA instruments were compared as well. Results: Twenty-seven eyes from 23 subjects diagnosed with CNV were analyzed. No significant differences were detected between manual and automatic measurements: SD-OCTA 3 × 3-mm (P = 0.61, paired t-test) and 6 × 6-mm (P = 0.09, paired t-test) scans and the SS-OCTA 3 × 3-mm (P = 0.41, paired t-test) and 6 × 6-mm (P = 0.16, paired t-test) scans. Bland-Altman analyses were performed to confirm the agreement between automatic and manual measurements. Mean lesion sizes were significantly larger for the SS-OCTA images compared with the SD-OCTA images: 3 × 3-mm scans (P = 0.011, paired sample t-test) and the 6 × 6-mm scans (P = 0.021, paired t-test). Conclusions: The automated algorithm measurements of CNV were in agreement with the hand-drawn measurements. On average, automated SS-OCTA measurements were larger than SD-OCTA measurements and consistent with the results from using hand-drawn measurements.

Comparison between Widefield En Face Swept-Source OCT and Conventional Multimodal Imaging for the Detection of Reticular Pseudodrusen.

PURPOSE: The ability to detect reticular pseudodrusen (RPD)/subretinal drusenoid deposits (SDDs) using 12×12-mm widefield en face swept-source optical coherence tomography (SS-OCT) imaging was compared with conventional multimodal imaging (color, fundus autofluorescence (FAF), and infrared reflectance [IR] imaging) in eyes with nonexudative age-related macular degeneration (AMD). DESIGN: Cross-sectional study. PARTICIPANTS: Patients with nonexudative AMD were prospectively enrolled in an SS-OCT imaging study at the Bascom Palmer Eye Institute. METHODS: On the same day, all participants underwent color, FAF, and IR fundus imaging, as well as imaging with a prototype Zeiss 100 kHz SS-OCT instrument (Carl Zeiss Meditec Inc, Dublin, CA). Two masked graders assessed the presence, absence, or uncertainty of RPD/SDDs on conventional multimodal images and separately on 4 different SS-OCT en face images derived from the same volumetric dataset. The results from grading the conventional images and the SS-OCT en face images were compared. MAIN OUTCOME MEASURES: Agreement in the detection of RPD/SDDs using different imaging modalities. RESULTS: A total of 307 eyes (209 patients) were graded for the presence or absence of RPD/SDDs. The agreement between SS-OCT and multimodal imaging was 83%. The difference in RPD/SDD detection with either image modality was not statistically significant (P = 0.21). The sensitivity of SS-OCT in RPD/SDD detection was 83%, and when using conventional imaging, the sensitivity was 75%. When using SS-OCT imaging alone, 10% of RPD/SDD cases would be missed, and when using conventional imaging alone, 14% of RPD/SDD cases would be missed. The presence of RPD/SDD was confirmed retrospectively in 48 of 52 cases once the overall grading was unmasked and the graders reevaluated the conventional multimodal images and the widefield SS-OCT en face images. CONCLUSIONS: All 4 imaging modalities used together provided the best strategy for the detection of RPD/SDDs. However, when using widefield en face SS-OCT slab imaging alone, the detection of RPD/SDDs was at least as good as conventional imaging.

Wide-field imaging of retinal vasculature using optical coherence tomography-based microangiography provided by motion tracking.

Optical coherence tomography (OCT)-based optical microangiography (OMAG) is a high-resolution, noninvasive imaging technique capable of providing three-dimensional in vivo blood flow visualization within microcirculatory tissue beds in the eye. Although the technique has demonstrated early clinical utility by imaging diseased eyes, its limited field of view (FOV) and the sensitivity to eye motion remain the two biggest challenges for the widespread clinical use of the technology. Here, we report the results of retinal OMAG imaging obtained from a Zeiss Cirrus 5000 spectral domain OCT system with motion tracking capability achieved by a line scan ophthalmoscope (LSO). The tracking LSO is able to guide the OCT scanning, which minimizes the effect of eye motion in the final results. We show that the tracking can effectively correct the motion artifacts and remove the discontinuities and distortions of vascular appearance due to microsaccade, leading to almost motion-free OMAG angiograms with good repeatability and reliability. Due to the robustness of the tracking LSO, we also show the montage scan protocol to provide unprecedented wide field retinal OMAG angiograms. We experimentally demonstrate a 12 x 16 mm² retinal OMAG angiogram acquired from a volunteer, which is the widest FOV retinal vasculature imaging up to now in the community.