Development and validation of a deep-learning model to predict 10-year atherosclerotic cardiovascular disease risk from retinal images using the UK Biobank and EyePACS 10K datasets.

Background: Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of death globally, and early detection of high-risk individuals is essential for initiating timely interventions. The authors aimed to develop and validate a deep learning (DL) model to predict an individual's elevated 10-year ASCVD risk score based on retinal images and limited demographic data. Methods: The study used 89,894 retinal fundus images from 44,176 UK Biobank participants (96% non-Hispanic White, 5% diabetic) to train and test the DL model. The DL model was developed using retinal images plus age, race/ethnicity, and sex at birth to predict an individual's 10-year ASCVD risk score using the pooled cohort equation (PCE) as the ground truth. This model was then tested on the US EyePACS 10K dataset (5.8% non-Hispanic White, 99.9% diabetic), composed of 18,900 images from 8969 diabetic individuals. Elevated ASCVD risk was defined as a PCE score of ≥7.5%. Results: In the UK Biobank internal validation dataset, the DL model achieved an area under the receiver operating characteristic curve of 0.89, sensitivity 84%, and specificity 90%, for detecting individuals with elevated ASCVD risk scores. In the EyePACS 10K and with the addition of a regression-derived diabetes modifier, it achieved sensitivity 94%, specificity 72%, mean error -0.2%, and mean absolute error 3.1%. Conclusion: This study demonstrates that DL models using retinal images can provide an additional approach to estimating ASCVD risk, as well as the value of applying DL models to different external datasets and opportunities about ASCVD risk assessment in patients living with diabetes.

Agreement and precision of wide and cube scan measurements between swept-source and spectral-domain OCT in normal and glaucoma eyes.

This study aimed to evaluate agreement of Wide scan measurements from swept-source optical coherence tomography (SS-OCT) Triton and spectral-domain OCT (SD-OCT) Maestro in normal/glaucoma eyes, and to assess the precision of measurements from Wide and Cube scans of both devices. Three Triton and three Maestro operator/device configurations were created by pairing three operators, with study eye and testing order randomized. Three scans were captured for Wide (12 mm × 9 mm), Macular Cube (7 mm × 7 mm-Triton; 6 mm × 6 mm-Maestro), and Optic Disc Cube (6 mm × 6 mm) scans for 25 normal eyes and 25 glaucoma eyes. Parameter measurements included circumpapillary retinal nerve fiber layer(cpRNFL), ganglion cell layer + inner plexiform layer (GCL+), and ganglion cell complex (GCL++). A two-way random effect analysis of variance model was used to estimate the repeatability and reproducibility; agreement was evaluated by Bland-Altman analysis and Deming regression. The precision estimates were low, indicating high precision, for all thickness measurements with the majority of the limits < 5 µm for the macula and < 10 µm for the optic disc. Precision of the Wide and Cube scans were comparable. Excellent agreement between the two devices was found for Wide scans, with the mean difference < 3 µm across all measurements (cpRNFL < 3 µm, GCL+ < 2 µm, GCL ++ < 1 µm), indicating interoperability. A single Wide scan covering the peripapillary and macular regions may be useful for glaucoma diagnosis and management.

Agreement and Precision of Wide and Cube Scan Measurements between Swept-source and Spectral-domain OCT in Normal and Glaucoma Eyes.

This study aimed to evaluate agreement of Wide scan measurements from swept-source optical coherence tomography(SS-OCT) Triton and spectral-domain OCT(SD-OCT) Maestro in normal/glaucoma eyes, and to assess the precision of measurements from Wide and Cube scans of both devices. Three Triton and three Maestro operator/device configurations were created by pairing three operators, with study eye and testing order randomized. Three scans were captured for Wide (12mm×9mm), Macular Cube (7mmx7mm-Triton; 6mmx6mm-Maestro), and Optic Disc Cube (6mmx6mm) scans for 25 normal eyes and 25 glaucoma eyes. Thickness of circumpapillary retinal nerve fiber layer(cpRNFL), ganglion cell layer+inner plexiform layer(GCL+), and ganglion cell complex(GCL++) was obtained from each scan. A two-way random effect analysis of variance model was used to estimate the repeatability and reproducibility; agreement was evaluated by Bland-Altman analysis and Deming regression. Precision limit estimates were low: <5µm for macular and <10µm for optic disc parameters. Precision for Wide and Cube scans of both devices were comparablein both groups. Excellent agreement between the two devices was found for Wide scans, with the mean difference<3µm across all measurements (cpRNFL<3µm, GCL+<2µm, GCL++<1µm), indicating interoperability. A single Wide scan covering the peripapillary and macular regions may be useful for glaucoma management.

Agreement, repeatability, and reproducibility of quantitative retinal layer assessment using swept-source and spectral-domain optical coherence tomography in eyes with retinal diseases.

Purpose: To evaluate the agreement and precision of retinal thickness measurements obtained using swept-source optical coherence tomography (SS-OCT) and spectral-domain OCT (SD-OCT) in healthy eyes and eyes with retinopathy. Methods: This cross-sectional prospective study involved three DRI-OCT Triton (SS-OCT) and three 3D-OCT-1 Maestro (SD-OCT) devices. One of each device (Maestro and Triton) was paired with a single operator. Healthy subjects and patients with retinal diseases were recruited, with study eye and testing order randomized. At least 3 scans per eye were captured for wide scan (12 mm × 9 mm-Triton and Maestro) and macular cube scan (7 mm × 7 mm-Triton, 6 mm × 6 mm-Maestro). Thickness of the full retina, ganglion cell layer + inner plexiform layer (GCL+), and ganglion cell complex (GCL++) were obtained from wide scan and cube scans. Agreement of the measurements between the Triton and Maestro was evaluated by Bland-Altman analysis and Deming regression for each group. Repeatability and reproducibility were assessed using a two-way random effect analysis of variance (ANOVA) model for each parameter by group. Results: Twenty-five healthy subjects (25 eyes) and 26 patients with retinal diseases (26 eyes), including, but not limited to, age-related macular degeneration, macular hole, and diabetic retinopathy were recruited. Overall, the measurement differences between Triton and Maestro were <6 µm (mean differences of full retina, GCL++, and GCL+ thickness were ≤5.5 µm, 1.3 µm, and 2.8 µm, respectively) and not statistically significant across the parameters. The repeatability and reproducibility estimates indicate high precision in both devices and groups. Across all the parameters, the repeatability limit was ≤7.6 µm for Triton and ≤12.7 µm for Maestro; reproducibility limit was ≤9.2 µm for Triton and ≤14.4 µm for Maestro. In eyes with retinal pathology, the repeatability coefficient of variation (CV)% was ≤2.6% for Triton and ≤3.4% for Maestro; reproducibility CV% was ≤3.3% for Triton and ≤3.5% for Maestro. Conclusion: Both Triton SS-OCT and Maestro SD-OCT provide reliable measurements of retinal thickness in healthy eyes and eyes with retinal diseases. Excellent agreement between the two devices indicates interoperability when testing healthy eyes or eyes with retinal pathology. These findings support the use of thickness measurements from Triton SS-OCT and Maestro SD-OCT in clinical practice.

Optical Coherence Tomography Measurements of the Retinal Pigment Epithelium to Bruch Membrane Thickness Around Geographic Atrophy Correlate With Growth.

PURPOSE: The retinal pigment epithelium (RPE) to Bruch membrane (BM) distance around geographic atrophy (GA) was measured using an optical attenuation coefficient (OAC) algorithm to determine whether this measurement could serve as a clinical biomarker to predict the annual square root enlargement rate (ER) of GA. DESIGN: A retrospective analysis of a prospective, observational case series. METHODS: Eyes with GA secondary to age-related macular degeneration (AMD) were imaged with swept-source OCT (SS-OCT) using a 6 × 6-mm scan pattern. GA lesions were identified and measured using customized en face OCT images, and GA annual square root ERs were calculated. At baseline, the OACs were calculated from OCT datasets to generate customized en face OAC images for GA visualization. RPE-BM distances were measured using OAC data from different subregions around the GA. RESULTS: A total of 38 eyes from 27 patients were included in this study. Measured RPE-BM distances were the highest in the region closest to GA. The RPE-BM distances immediately around the GA were significantly correlated with GA annual square root ERs (r = 0.595, P < .001 for a 0- to 300-µm rim around the GA). No correlations were found between RPE-BM distances and previously published choriocapillaris (CC) flow deficits in any subregions. CONCLUSIONS: RPE-BM distances from regions around the GA significantly correlate with the annual ERs of GA. These results suggest that an abnormally thickened RPE/BM complex contributes to GA growth and that this effect is independent of CC perfusion deficits.

Choroidal Changes in Eyes With Polypoidal Choroidal Vasculopathy After Anti-VEGF Therapy Imaged With Swept-Source OCT Angiography.

Purpose: Swept-source optical coherence tomography angiography was used to investigate choroidal changes and their association with pigment epithelial detachments (PEDs) in eyes with polypoidal choroidal vasculopathy (PCV) after treatment with vascular endothelial growth factor (VEGF) inhibitors. Methods: Patients with treatment-naïve PCV were included and underwent anti-VEGF therapy. Mean choroidal thickness (MCT), choroidal vascularity index (CVI), and PED volume measurements were obtained before and after treatment. Results: Thirty-four treatment-naïve PCV eyes from 33 patients were included. The PED volume decreased after treatment (P < 0.05). The MCT decreased from 223.0 ± 79.6 µm at baseline to 210.9 ± 76.2 µm after treatment (P < 0.001). The CVI at baseline was 0.599 ± 0.024, and the CVI after treatment was 0.602 ± 0.023 (P = 0.16). There was a correlation between the decreased PED volumes and the decreased MCT measurements (r = 0.47; P = 0.006). Also, there was a correlation between the decreased PED volumes and the increased CVI measurements (r = -0.63; P < 0.001). Conclusions: In treatment-naïve eyes with PCV, the decreases in PED volumes were correlated with the decrease in MCT and the increase in CVI measurements. We propose that, at baseline, the PCV lesions serve as high-volume arteriovenous shunts between choroidal arterial and venous circulation, causing transudation into the choroidal stroma. We propose that, after treatment, the blood flow through the vascular shunt is reduced, the excess stromal transudation is resorbed, and the exudation from the neovascular lesion is reduced, resulting in thinning of the choroid, resolution of the PEDs, and an increase in the CVI due to the resorption of excess choroidal transudation.

Student becomes teacher: training faster deep learning lightweight networks for automated identification of optical coherence tomography B-scans of interest using a student-teacher framework.

This work explores a student-teacher framework that leverages unlabeled images to train lightweight deep learning models with fewer parameters to perform fast automated detection of optical coherence tomography B-scans of interest. Twenty-seven lightweight models (LWMs) from four families of models were trained on expert-labeled B-scans (∼70 K) as either "abnormal" or "normal", which established a baseline performance for the models. Then the LWMs were trained from random initialization using a student-teacher framework to incorporate a large number of unlabeled B-scans (∼500 K). A pre-trained ResNet50 model served as the teacher network. The ResNet50 teacher model achieved 96.0% validation accuracy and the validation accuracy achieved by the LWMs ranged from 89.6% to 95.1%. The best performing LWMs were 2.53 to 4.13 times faster than ResNet50 (0.109s to 0.178s vs. 0.452s). All LWMs benefitted from increasing the training set by including unlabeled B-scans in the student-teacher framework, with several models achieving validation accuracy of 96.0% or higher. The three best-performing models achieved comparable sensitivity and specificity in two hold-out test sets to the teacher network. We demonstrated the effectiveness of a student-teacher framework for training fast LWMs for automated B-scan of interest detection leveraging unlabeled, routinely-available data.

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.

Validation of a Novel Automated Algorithm to Measure Drusen Volume and Area Using Swept Source Optical Coherence Tomography Angiography.

Purpose: The purpose of this study was to validate a novel automated swept source optical coherence tomography angiography (SS-OCTA) algorithm to measure elevations of the retinal pigment epithelium (RPE) in eyes with nonexudative age-related macular degeneration (neAMD). Methods: Patients with drusen were enrolled in a prospective optical coherence tomography (OCT) study and underwent both spectral domain OCT (SD-OCT) and SS-OCTA imaging at the same visit using the 6 × 6 mm scan patterns. The RPE elevation measurements (square root area and cube root volume) from the SS-OCTA algorithm were compared with the automated validated SD-OCT algorithm on the instrument. Standard deviations of drusen measurements from four repeated scans of another separate set were also calculated to evaluate the reproducibility of the SS-OCTA algorithm. Results: A total of 53 eyes from 28 patients were scanned on both instruments. A very strong correlation was found between the measurements from the two algorithms (all r > 0.95), although the measurements of the drusen area and volume were all larger from the SS-OCTA instrument. The reproducibility of the new SS-OCTA algorithm was analyzed using a sample of 66 eyes from 43 patients. The intraclass correlation coefficient (ICC) was greater than 99% from different macular regions for both the square root area and cube root volume measurements. Conclusions: A novel automated SS-OCTA algorithm for the quantitative assessment of drusen was validated against the SD-OCT algorithm and was shown to be highly reproducible. Translational Relevance: This novel SS-OCTA algorithm provides a strategy to measure the area and volume of drusen to assess disease progression in neAMD.

Swept-Source OCT Angiographic Characteristics of Treatment-Naïve Nonexudative Macular Neovascularization in AMD Prior to Exudation.

Purpose: To investigate the characteristics of treatment-naïve nonexudative macular neovascularization (MNV) in age-related macular degeneration before the onset of exudation using swept-source optical coherence tomography angiography. Methods: MNV area, choriocapillaris (CC) flow deficits (FDs), vessel area density (VAD), vessel skeleton density (VSD), retinal pigment epithelial detachment (PED) volume, mean choroidal thickness (MCT), and choroid vascularity index (CVI) measurements were assessed at two visits prior to exudation. We compared measurements made at the second visit and the rate of change between visits in eyes with and without exudation. The differences in these parameters between eyes with and without subsequent exudation were summarized with 95% confidence intervals (CIs). Results: Twenty-one eyes with nonexudative MNV were identified and followed. Nine eyes developed exudation, and 12 eyes did not develop exudation. Differences between these groups of eyes for all parameters tended to be small, and the 95% CIs largely ruled out any substantial differences. Overall, eyes with exudation had 24% smaller VAD, 20% smaller VSD, and 33% smaller PED volume measurements. No noteworthy differences were observed for MNV area, CC FDs, MCT, or CVI measurements. Conclusions: The onset of exudation was correlated with lesions having less vascularity and smaller PED volume measurements, but measurements of MNV area, CC FDs, MCT, and CVI were not correlated with near-term exudation. Investigations are ongoing to further explore these and other anatomic changes as harbingers of near-term exudation.

Correlations Between Choriocapillaris and Choroidal Measurements and the Growth of Geographic Atrophy Using Swept Source OCT Imaging.

PURPOSE: Correlations among enlargement rates (ERs) of geographic atrophy (GA) and choriocapillaris (CC) flow deficits (FDs), mean choroidal thickness (MCT), and choroidal vascularity index (CVI) were investigated using swept source-optical coherence tomography (SS-OCT) in age-related macular degeneration (AMD). DESIGN: A retrospective review of prospective, observational case series. METHODS: Eyes with GA from AMD were imaged with SS-OCT using 6 × 6-mm scan pattern. GA lesions were identified and measured using customized en face structural images, and annual square root ERs of GA were calculated. At baseline, choriocapillaris FDs from different regions outside the GA were measured, and MCT and CVI from the entire scan area were measured. All measurements were performed using previously published and validated algorithms. RESULTS: A total of 38 eyes from 27 patients were included. The CC FDs within each region around GA lesions were highly correlated with ERs of GA (all P < .005). CVI inside the GA region was correlated with the ERs (P = .03), whereas other choroidal measurements had no significant correlation with the ERs of GA (P > .06). CONCLUSIONS: Statistically significant correlations were found between the ERs of GA and CC percentage of FD (FD%) from the entire scan region outside the GA and not just the region immediately adjacent to the GA. These results suggest that abnormal CC perfusion throughout the macula contributes to disease progression in eyes with GA. CVI inside the GA region could also be a potential indicator for the growth of GA.

Effects of Induced Astigmatism on Spectral Domain-OCT Angiography Quantitative Metrics.

PURPOSE: To analyze the effect of induced astigmatism on en-face spectral-domain optical coherence tomography angiography quantitative metrics. DESIGN: Prospective crossover study. METHODS: Normal eyes without astigmatism and with 0.75, 1.75, and 2.75 diopters (D) of with-the-rule (WTR) astigmatism were imaged using a 3 × 3-mm scan pattern SD-OCTA CIRRUS 5000 HD-OCT with AngioPlex (Carl Zeiss Meditec, Dublin, CA, USA). Quantitative parameters, including foveal avascular zone metrics, parafoveal vessel length density (VD), and perfusion density (PD) were corrected for magnification secondary to axial length and analyzed. Univariate linear regressions were performed within each eye to correlate quantitative metrics to the level of an induced astigmatic cylinder. RESULTS: Fifteen eyes from 15 patients were imaged. Every 1-D increase in induced WTR astigmatism was associated with a statistically significant decrease in VD and PD within all Early Treatment Diabetic Retinopathy Study inner ring quadrants; however, especially more so nasally (VD: 0.63; P < .001; PD: 0.0089; P = .001). For every 1-D increase in induced astigmatism, the resulting decrease in the inner ring superior quadrant was 12% greater for VD and 16% greater for PD versus that in the inferior quadrant. The resulting decrease in the inner ring nasal quadrant was 40% greater for VD and 48% greater for PD versus that in the temporal quadrant. CONCLUSIONS: Increasing levels of induced WTR astigmatism correlated with globally diminishing VD and PD, was more symmetrical for vertical than horizontal quadrants, and was most pronounced nasally. This may be due to a high prevalence of horizontally oriented vessels nasally and the horizontal optical defocus induced by WTR astigmatism.

Validation of a Compensation Strategy Used to Detect Choriocapillaris Flow Deficits Under Drusen With Swept Source OCT Angiography.

PURPOSE: A compensation strategy that was developed to measure the choriocapillaris (CC) flow deficits (FDs) under drusen was tested in eyes with large drusen from age-related macular degeneration (AMD) before and after the drusen spontaneously resolved without evidence of disease progression. DESIGN: Prospective, observational consecutive case series. METHODS: Patients with AMD were enrolled in a prospective swept-source optical coherence tomography (SS-OCT) imaging study. Consecutive eyes with large drusen were followed, and eyes that underwent spontaneous collapse of drusen without evidence of disease progression were identified retrospectively. The drusen-resolved regions were manually outlined. CC FDs were measured using a previously published compensation strategy that adjusted for the decreased signal intensity underlying drusen. Both the percentage of FDs (FD%) and the mean FD sizes (MFDSs) were measured before and after drusen resolution. RESULTS: Resolution of drusen was identified in 8 eyes from 8 patients. The average interval between the 2 visits was 7.8 months. The average drusen volumes measured between visits were 0.23 and 0.04 mm3, respectively. After the drusen resolved, the average follow-up time without evidence of disease progression was 10.1 months. When the 2 visits were compared, there were no statistically significant differences in any of the CC parameters within the drusen resolved regions once the compensation strategy was applied (all P values >.22). CONCLUSIONS: In this naturally occurring experiment in which drusen collapsed without evidence of disease progression, the CC parameters were similar once our compensation strategy was applied both before and after the drusen resolved.

Age-Related Changes in Choroidal Thickness and the Volume of Vessels and Stroma Using Swept-Source OCT and Fully Automated Algorithms.

PURPOSE: To determine age-related changes in choroidal thickness and the volume of choroidal vessels and stroma using automated algorithms based on structural swept-source OCT (SS-OCT) scans. DESIGN: Prospective and observational study. PARTICIPANTS: The study included 144 normal participants with ages ranging from 20 to 88 years. METHODS: A previously reported strategy was used to automatically segment the choroid using SS-OCT structural images. Attenuation correction was applied on B-scans to enhance the choroidal contrast and facilitate more accurate automatic segmentation of the 3-dimensional choroidal vessel and stroma. The parameters that we investigated included mean choroidal thickness (MCT), choroidal vessel volume (CVV), choroidal stroma volume (CSV), choroid vascularity index (CVI), and the choroidal stroma-to-vessel volume ratio (CSVR). Correlations between MCT and choroidal vessel metrics of CVV, CSV, CVI, and CSVR were studied. Regional distributions of MCT and CVI were analyzed using a grid centered on the fovea. Age-related changes in MCT, CVV, CSV, and CVI were studied in the entire scanning region, as well as in the subregions of the grids. MAIN OUTCOME MEASURES: Age-related changes in MCT, CVV, CSV, and CVI using 6×6-mm and 12×12-mm SS-OCT scans. RESULTS: The automated choroid segmentations were validated against manual segmentations, and MCT measurements were shown to be in good agreement (P < 0.0001). Choroidal vessel volume and CSV showed significant correlations with MCT (all P < 0.0001). Interestingly, CVI and CSVR were constant, with little variation among all participants regardless of age and MCT (61.1±1.8% and 0.64±0.05, respectively). Measurements on 12×12-mm and 6×6-mm scans showed excellent agreement in all scan regions (all P < 0.0001). While choroidal thickness and choroidal volume, which includes both choroidal vessels and stroma, decrease with age (all P < 0.0001), the CVI and CSVR vary little among all ages in all regions. CONCLUSIONS: Whereas MCT, CVV, and CSV decrease with age, the CVI and CSVR remain constant in all regions with age. Ongoing studies are using these automated algorithms on SS-OCT structural datasets to investigate the diagnostic usefulness of these choroidal parameters in a myriad of ocular and systemic diseases.

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.

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.

Correlations between Choriocapillaris Flow Deficits around Geographic Atrophy and Enlargement Rates Based on Swept-Source OCT Imaging.

PURPOSE: To determine the possible correlation between the annual enlargement rates (ERs) of geographic atrophy (GA) with the percentage and size of the choriocapillaris (CC) flow deficits (FDs) surrounding GA, measured with swept-source OCT angiography (SS-OCTA) images. DESIGN: Prospective, observational case series. PARTICIPANTS: Patients with GA secondary to nonexudative AMD. METHODS: Patients were imaged with a 100-kHz SS-OCTA instrument (PLEX Elite 9000, Carl Zeiss Meditec, Dublin, CA) using a 6×6-mm field of view scan pattern. The GA area measurements were obtained from en face SS-OCT sub-retinal pigment epithelium (RPE) slab images. Visualization of the CC and quantification of FDs were performed using a previously published validated algorithm based on a 20-µm thickness slab with the inner boundary located beneath Bruch's membrane. The percentage of CC FDs (FD%) and the average FD area measurements were calculated in different regions around the GA. MAIN OUTCOME MEASURES: The correlation between the CC FDs and the ERs of GA. RESULTS: Twenty-two eyes from 15 patients were eligible for the analysis. The annual square root ERs for GA ranged from 0.07 to 0.75 mm/year. The CC FD% and average FD area measurements were highly correlated with each other (P < 0.001), with the highest FD values found in the region closest to the margin of GA. The ERs correlated best with the average CC FD area measurements in the total scan area minus the area of GA (Pearson r = 0.747; P < 0.001) than those in the regions immediately surrounding the GA (r = 0.544; P = 0.009). CONCLUSIONS: Contrary to expectations, the global CC FD measurements had a better correlation with the ERs of GA than those in the regions immediately around the GA. The most likely explanation for this outcome is that normal age-related increases in FDs within the central macula confound the correlations between the ERs of GA and FDs, whereas the regions furthest away from the margins of GA are less affected by normal age-related changes and reflect FD alterations related to AMD severity.

Effect of Scan Size on Glaucoma Diagnostic Performance Using OCT Angiography En Face Images of the Radial Peripapillary Capillaries.

PRECIS: When comparing 4.5×4.5 mm to 6.0×6.0 mm optical coherence tomography angiography scans of the radial peripapillary capillaries (RPCs) for glaucoma diagnostic capability, there was a trend of 4.5 scans outperforming 6.0 scans, especially for inferior, nasal, and superior quadrants. OBJECTIVES: The main purpose of this study was to compare diagnostic ability of peripapillary vessel parameters from 4.5×4.5 mm (4.5) and 6.0×6.0 mm (6.0) spectral-domain optical coherence tomography angiography scans of the RPC in detecting primary open-angle glaucoma from nonglaucoma eyes. METHODS: Consecutive patients from an academic glaucoma clinic underwent 4.5 and 6.0 scans (CIRRUS HD-OCT 5000 with AngioPlex OCT Angiography; ZEISS, Dublin, CA). Automatic segmentation created en face RPC images. Vessel area density, vessel skeleton density, and flux were calculated using custom quantification software, and perfusion density and flux index (FI) using automated quantification software. Area under the curve statistics included age and hypertension in the analysis. RESULTS: Of 173 eyes from 123 patients who underwent both 4.5 and 6.0 imaging, 32 primary open-angle glaucoma eyes from 32 patients and 95 nonglaucoma eyes from 95 patients were studied. For the global region of 4.5 versus 6.0 scans, area under the curve was 0.940 and 0.916 for vessel area density (P=0.286); 0.941 and 0.921 for vessel skeleton density (P=0.385); 0.942 and 0.916 for flux (P=0.239); 0.912 and 0.884 for perfusion density (P=0.103); and 0.913 and 0.865 for FI (P=0.159), respectively. For the quadrant regions, 4.5 images significantly outperformed 6.0 images for the superior and inferior quadrants for flux and superior and nasal quadrants for FI (P-values=0.007, 0.047, 0.011, 0.007, respectively); other quadrant differences were not significant. CONCLUSIONS: Parameters from 4.5 scans generally outperformed those from 6.0 scans in the global and quadrant regions, suggesting greater digital resolution in 4.5 scans of the immediate peripapillary RPC is important in detecting glaucomatous changes.

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.