Correlations Between Different Choriocapillaris Flow Deficit Parameters in Normal Eyes Using Swept Source OCT Angiography.

PURPOSE: Choriocapillaris (CC) imaging of normal eyes with swept-source optical coherence tomographic angiography (SS-OCTA) was performed, and the percentage of CC flow deficits (FD%) and the average area of CC flow deficits (FDa) were compared within the given macular regions. DESIGN: A prospective, cross-sectional study. METHODS: Subjects with normal eyes ranging in age from their 20s through their 80s were imaged with SS-OCTA (PLEX Elite 9000; Carl Zeiss Meditec, Dublin, California, USA) using both 3×3-mm and 6×6-mm macular scan patterns. The CC images were generated using a previously published and validated algorithm. In both 3×3-mm and 6×6-mm scans, the CC FD% and FDa were measured in circular regions centered on the fovea with diameters as 1 mm and 2.5 mm (C1 and C2.5). In 6×6-mm scans, the FD% and FDa were measured within an additional circular region with diameter as 5 mm (C5). The correlations between FD% and FDa from each region were analyzed with Pearson correlation coefficients. RESULTS: A total of 164 eyes were analyzed. There was excellent correlation between CC FDa and FD% measurements from each region. In the 3×3-mm scans, the correlations in the C1 and C2.5 regions were 0.83 and 0.90, respectively. In the 6×6-mm scans, the correlations in C1, C2.5, and C5 regions were 0.90, 0.89, and 0.89, respectively. CONCLUSIONS: When measuring CC FDs, we found excellent correlations between FDa and FD% in regions from 3×3-mm and 6×6-mm scans. Further studies are needed to determine if one parameter is more useful when studying diseased eyes.

Widefield Swept-Source Optical Coherence Tomography Angiography of Proliferative Diabetic Retinopathy.

BACKGROUND AND OBJECTIVE: To demonstrate the utility of widefield swept-source optical coherence tomography angiography (SS-OCTA) for the diagnosis and management of proliferative diabetic retinopathy (PDR). PATIENTS AND METHODS: Consecutive patients with vision-threatening diabetic retinopathy were imaged with widefield SS-OCTA using the 12 mm × 12 mm scan pattern. RESULTS: Twenty-four eyes of 12 patients underwent SS-OCTA imaging. In all 24 eyes, the en face total retinal flow images detected areas of decreased retinal perfusion, and the en face vitreoretinal interface (VRI) slabs detected foci of retinal neovascularization (NV). NV was treated and followed using the VRI images. CONCLUSIONS: Widefield SS-OCTA is a useful, noninvasive technology for the detection and monitoring of NV in PDR. Features of interest, such as areas of decreased retinal perfusion, increased retinal thickness, and NV, can be identified from different en face slabs extracted from a single 12 mm × 12 mm scan. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:474-484.].

Two-Year Risk of Exudation in Eyes with Nonexudative Age-Related Macular Degeneration and Subclinical Neovascularization Detected with Swept Source Optical Coherence Tomography Angiography.

PURPOSE: Swept source optical coherence tomography angiography (SS-OCTA) was used to study the prevalence, incidence, and natural history of subclinical macular neovascularization (MNV) in eyes with unilateral nonexudative age-related macular degeneration. DESIGN: Prospective cohort study. METHODS: Patients were imaged using 3- × 3-mm and 6- × 6-mm SS-OCTA scan patterns. MNV was detected using the outer retina to choriocapillaris en face slab. Prevalence and incidence of subclinical MNV, Kaplan-Meier cumulative estimates for the overall risk of exudation, and the association between neovascular lesion size and the risk of exudation were assessed through 2 years. RESULTS: From August 2014 through March 2018, 227 patients (154 intermediate and 73 late age-related macular degeneration eyes) underwent SS-OCTA imaging. Thirty eyes (13.2%) had subclinical MNV at first imaging and 12 eyes (8.9%) developed subclinical MNV during follow-up. Of the 191 eyes with >1 visit, 19 developed exudation. Fourteen of these eyes had pre-existing subclinical MNV. The incidence of exudation from the time of first detection of any subclinical MNV was 34.5%. The relative risk of exudation after detection of subclinical MNV was 13.6 times greater (95% confidence interval 4.9-37.7) than in the absence of subclinical MNV (P < .001). There was no significant risk of exudation based on lesion size alone (P = .91). CONCLUSIONS: By 24 months, the risk of exudation was 13.6 times greater for eyes with subclinical MNV detected by SS-OCTA compared with eyes without subclinical MNV. For eyes with subclinical MNV in the absence of symptomatic exudation, we recommend close follow-up without treatment.

Predictive Value of the OCT Double-Layer Sign for Identifying Subclinical Neovascularization in Age-Related Macular Degeneration.

PURPOSE: Structural OCT images from eyes with nonexudative age-related macular degeneration (AMD) were graded for the presence of a double-layer sign to determine if the double-layer sign predicted subclinical macular neovascularization (MNV). DESIGN: Prospective, observational study. PARTICIPANTS: Nonexudative AMD patients with and without subclinical MNV identified by swept-source (SS) OCT angiography (OCTA). METHODS: Participants were enrolled prospectively into an SS OCTA imaging study. A set of test scans with and without subclinical MNV was compiled to assess the ability of trained graders to identify nonexudative type 1 MNV. The graders evaluated only the structural OCT B-scans of those eyes. The presence of a double-layer sign was used as a predictive sign for subclinical type 1 MNV. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) from 2 separate gradings were calculated and compared. MAIN OUTCOME MEASURES: The association between the presence of a double-layer sign and subclinical type 1 MNV. RESULTS: One hundred eyes with nonexudative AMD from 94 patients were used for this study. The test set contained 64 eyes with intermediate AMD, which included 20 eyes with subclinical MNV, and 36 eyes with late AMD, which included 13 eyes with subclinical MNV. Two junior graders read the scans separately then reached a consensus grading. They detected a double-layer sign in 24 of 33 eyes with subclinical MNV and did not detect a double-layer sign in 56 of 67 eyes without MNV. Their sensitivity, specificity, PPV, and NPV were 73%, 84%, 69%, and 86%, respectively. The senior grader detected a double-layer sign in 29 of 33 eyes with subclinical MNV and did not detect a double-layer sign in 58 of 67 eyes without MNV, achieving a sensitivity, specificity, PPV, and NPV of 88%, 87%, 76%, and 94%, respectively. For all graders, there were statistically significant associations between type 1 MNV and presence of the double-layer sign (P < 0.001). CONCLUSIONS: Presence of the double-layer sign on structural OCT B-scans was associated with subclinical type 1 MNV and can be used to identify these lesions with good predictive values in eyes with nonexudative AMD.

En Face Imaging of Geographic Atrophy Using Different Swept-Source OCT Scan Patterns.

PURPOSE: Different swept-source (SS) OCT scan patterns were used to image geographic atrophy (GA) to determine if they provided similar area and enlargement measurements in eyes with age-related macular degeneration (AMD). DESIGN: Prospective, observational case series. PARTICIPANTS: Patients with GA secondary to nonexudative AMD. METHODS: Patients were imaged using SS OCT (PLEX Elite 9000; Carl Zeiss Meditec, Dublin, CA), with follow-up imaging performed after 6 months and 1 year. Both the 6×6 mm and 12×12 mm scan patterns were obtained at each visit. Area measurements of GA were obtained from the en face images generated from a slab with boundaries extending 64 to 400 µm beneath Bruch's membrane. MAIN OUTCOME MEASURES: Comparison of area measurements and enlargement rates (ERs) measurements between the 6×6 mm and 12×12 mm scan patterns. RESULTS: Thirty-two eyes of 25 patients with GA secondary to nonexudative AMD were enrolled. The mean lesion area measurements at baseline were 3.81 mm2 for the 6×6 mm scan and 3.75 mm2 for the 12×12 mm scan. At baseline and over 1 year, the lesion area measurements between the 6×6 mm and the 12×12 mm scan patterns were comparable for all eyes (0.04 mm2; P < 0.001, analysis of variance). The annual ER measurements from the 6×6 mm and 12×12 mm scan patterns were similar (Pearson r = 0.99), with an average ER using the square root transformation strategy of 0.3 mm/year. CONCLUSIONS: Both the 6×6 mm and the 12×12 mm scan patterns resulted in similar area and ER measurements for GA when visualized using the en face images. With the 12×12 mm scan pattern, which represents a 40° field of view (FOV), the measurement of GA using OCT en face imaging is no longer limited by the 6×6 mm FOV. Since macular GA can extend beyond the 6×6 mm FOV, the 12×12 mm FOV can now image all macular GA. With a FOV now similar to autofluorescence and color fundus imaging, SS OCT imaging can be used as the sole imaging method for the detection, measurement, and ER assessment of all GA associated with AMD in clinical practice and in clinical trials.

Age-dependent Changes in the Macular Choriocapillaris of Normal Eyes Imaged With Swept-Source Optical Coherence Tomography Angiography.

PURPOSE: Swept-source optical coherence tomography angiography (SS-OCTA) was used to measure the age-dependent changes in macular choriocapillaris (CC) flow deficits (FDs) in normal eyes. DESIGN: A prospective, cross-sectional study. METHODS: Subjects with normal eyes ranging in age from their 20s to their 80s were imaged using a 100-kHz SS-OCTA instrument (PLEX Elite 9000, Carl Zeiss Meditec, Dublin, California, USA). Both 3 × 3-mm and 6 × 6-mm scans were used to image the macular CC. Visualization of the CC and quantification of FDs were performed using a previously validated algorithm. The percentage of FDs (FD%) in the central 1-mm circle (C1), 1.5-mm rim (R1.5), and 2.5-mm circle (C2.5) from the 3 × 3-mm and 6 × 6-mm scans and FD% in the 2.5-mm rim (R2.5) and 5-mm circle (C5) from the 6 × 6-mm scans were measured and correlated with age and axial length. RESULTS: A total of 164 subjects were enrolled, with at least 10 subjects from each decade of life. No meaningful correlations were found between FD% and axial length (|r| < 0.30). FD% in all fields increased with increasing age (all r > 0.50; all P < .001); however, the greatest increases were found in the central macula C1 regions and the smallest increases in the peripheral macula R2.5 regions. CONCLUSIONS: In normal aging, the FD% increased with age across the central 5 mm of the macula, but the greatest increase was found in the central 1-mm region of the macula.

Swept-Source Optical Coherence Tomography Angiography of an Amalric Choroidal Infarction in a Rare Presentation of Giant Cell Arteritis With Bilateral Corneal Edema.

A 73-year-old woman with 2 weeks of progressive painless vision loss was found to have bilateral corneal edema, jaw claudication, and temporal headache. Multimodal imaging revealed an Amalric choroidal infarct in the left eye visualized by widefield indocyanine green angiography and swept-source optical coherence tomography angiography (SS-OCTA). Prompt intravenous corticosteroid treatment resulted in 20/20 vision, and giant cell arteritis (GCA) was confirmed by a temporal artery biopsy. The case underscores the use of widefield SS-OCTA as a non-invasive test to aid in the diagnosis of GCA, as well as bilateral cornea edema as a rare presentation of GCA. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e157-e160.].

Anatomic Localization of Type 1 and Type 2 Macular Neovascularization Using Swept-Source OCT Angiography.

BACKGROUND AND OBJECTIVE: Swept-source optical coherence tomography angiography (SS-OCTA) and different boundary-specific segmentation strategies were used to distinguish type 1 macular neovascularization (MNV) from type 2 MNV in eyes with exudative age-related macular degeneration (AMD). PATIENTS AND METHODS: Eyes with exudative AMD were enrolled in a prospective study. Segmentation strategies included a slab from the outer retina (OR) to the choriocapillaris (CC) for the entire MNV, a slab from the retinal pigment epithelium (RPE) to the CC for the type 1 MNV, and a slab from the OR to the RPE for the type 2 MNV. RESULTS: In 13 eyes, SS-OCTA B-scans and en face images using different segmentation strategies were able to identify type 1 and type 2 components of the MNV. CONCLUSION: In eyes with exudative AMD, SS-OCTA imaging and commercially available boundary-specific segmentation strategies were used to distinguish between type 1 and type 2 MNV. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:878-886.].

Accurate estimation of choriocapillaris flow deficits beyond normal intercapillary spacing with swept source OCT angiography.

BACKGROUND: To estimate choriocapillaris flow deficits beyond normal intercapillary distance with swept source optical coherence tomography angiography (SS-OCTA). METHODS: Subjects were enrolled and repeated SS-OCTA scans were performed using the 3 mm × 3 mm scan pattern. Blood flow was identified using the complex optical microangiography (OMAGc) algorithm. The choriocapillaris (CC) was defined as a 20 µm slab of the flow volume beneath the outer boundary of Bruch's membrane (BM) and was compensated with the corresponding structural image for flow deficits measurement. Flow deficits were segmented based on one mean standard deviation from a normal database. A histogram based thresholding method was developed to remove small flow deficits that were determined by examining intercapillary spacing within normal CC networks. A registration method based on affine and B-spline transformation was utilized for the CC angiogram averaging. Four repeated scans were averaged, and results were compared with and without removal of small flow deficits after averaging a different number of scans (N=1, group 1; N=2, group 2; N=3, group 3 and N=4, group 4). RESULTS: Seven normal subjects were enrolled. Intercapillary distance was found to be 24 µm for the CC networks under OCTA, which was used as the threshold to exclude small flow deficits for CC quantification. After averaging, significant reduction in background noise and improvement in continuity of blood vessel networks were observed both on retinal and choriocapillaris angiograms. Flow deficit percentages of the choriocapillaris were significantly reduced with averaging (group 1 vs. group 2: P<0.0001; group 2 vs. group 3: P<0.001; group 3 vs. group 4: P<0.001). The flow deficit percentages were also significantly reduced after removing the small flow deficits (≤24 µm in diameter) in all groups (P<0.01). A statistically significant difference was found after removing small flow deficits (≤24 µm in diameter) between group 1 and group 2 (P<0.001), between group 2 and group 3 (P<0.05), and between group 3 and group 4 (P<0.05). However, the significance was decreased compared to that without small flow deficits removal. CONCLUSIONS: A method was developed to improve the robust estimation of choriocapillaris flow deficits by removing the small flow deficits corresponding to normal intercapillary spacing. After the removal of small flow deficits, fewer repeats were required for image averaging to achieve comparable accuracy of flow deficit measurements with SS-OCTA.

OCT Angiography Helps Distinguish Between Proliferative Macular Telangiectasia Type 2 and Neovascular Age-Related Macular Degeneration.

BACKGROUND AND OBJECTIVE: To demonstrate the advantage of optical coherence tomography angiography (OCTA) for the diagnosis and management of proliferative macular telangiectasia type 2 (MacTel2) masquerading as neovascular age-related macular degeneration (AMD). PATIENTS AND METHODS: This is an observational cases series. Three patients referred with the diagnosis of neovascular AMD were identified in this retrospective study. In addition to color fundus, fluorescein angiography, and spectral-domain OCT (SD-OCT) imaging, SD-OCTA (AngioPlex; Carl Zeiss Meditec, Dublin, CA) was performed. RESULTS: SD-OCTA revealed bilateral parafoveal retinal microvascular changes in three patients and unambiguously confirmed the diagnosis of MacTel2. CONCLUSION: OCTA is an important tool for the correct diagnosis of MacTel2 in older patients with the concomitant or masquerading diagnosis of AMD. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:303-312.].

Swept-Source OCT Angiography Identifies Choroidal Neovascularization Arising From a Choroidal Nevus.

Swept-source optical coherence tomography angiography (SS-OCTA) was used to diagnose choroidal neovascularization (CNV) arising from a choroidal nevus. A 61-year-old woman initially presented with submacular hemorrhage. She was diagnosed with neovascular age-related macular degeneration (AMD) and received three injections of bevacizumab (Avastin; Genentech, South San Francisco, CA). At a follow-up visit, SS-OCTA showed that the CNV appeared to arise from an adjacent choroidal nevus. This is the first report of using SS-OCTA to diagnose CNV associated with a choroidal nevus masquerading as neovascular AMD. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:360-363.].

A Novel Strategy for Quantifying Choriocapillaris Flow Voids Using Swept-Source OCT Angiography.

Purpose: To achieve reproducible imaging of the choriocapillaris and associated flow voids using swept-source OCT angiography (SS-OCTA). Methods: Subjects were enrolled and SS-OCTA was performed using the 3 × 3 mm scan pattern. Blood flow was identified using the complex optical microangiography (OMAG) algorithm. The choriocapillaris was defined as a slab from the outer boundary of Bruch's membrane (BM) to approximately 20 µm below BM. Compensation for the shadowing effect caused by the RPE and BM complex on the choriocapillaris angiogram was achieved by using the structural information from the same slab. A thresholding method to calculate the percentage of flow voids from a region was developed based on a normal database. Results: Twenty normal subjects and 12 subjects with drusen were enrolled. SS-OCTA identified the choriocapillaris in normal subjects as a lobular plexus of capillaries in the central macula and the lobular arrangement became more evident toward the periphery. In all eyes, signal compensation resulted in fewer choriocapillaris flow voids with improved repeatability of measurements. The best repeatability for the measurement was achieved by using 1 standard deviation (SD) for the thresholding strategy. Conclusions: SS-OCTA can image the choriocapillaris in vivo, and the repeatability of flow void measurements is high in the presence of drusen. The ability to image the choriocapillaris and associated flow voids should prove useful in understanding disease onset, progression, and response to therapies.

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.