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.

Fully Automated Prediction of Geographic Atrophy Growth Using Quantitative Spectral-Domain Optical Coherence Tomography Biomarkers.

PURPOSE: To develop a predictive model based on quantitative characteristics of geographic atrophy (GA) to estimate future potential regions of GA growth. DESIGN: Progression study and predictive model. PARTICIPANTS: One hundred eighteen spectral-domain (SD) optical coherence tomography (OCT) scans of 38 eyes in 29 patients. METHODS: Imaging features of GA quantifying its extent and location, as well as characteristics at each topographic location related to individual retinal layer thickness and reflectivity, the presence of pathologic features (like reticular pseudodrusen or loss of photoreceptors), and other known risk factors of GA growth, were extracted automatically from 118 SD OCT scans of 38 eyes from 29 patients collected over a median follow-up of 2.25 years. We developed and evaluated a model to predict the magnitude and location of GA growth at given future times using the quantitative features as predictors in 3 possible scenarios. MAIN OUTCOME MEASURES: Potential regions of GA growth. RESULTS: In descending order of out-of-bag feature importance, the most predictive SD OCT biomarkers for predicting the future regions of GA growth were thickness loss of bands 11 through 14 (5.66), reflectivity of bands 11 and 12 (5.37), thickness of reticular pseudodrusen (5.01), thickness of bands 5 through 11 (4.82), reflectivity of bands 7 through 11 (4.78), GA projection image (4.73), increased minimum retinal intensity map (4.59), and GA eccentricity (4.49). The predicted GA regions in the 3 tested scenarios resulted in a Dice index mean ± standard deviation of 0.81±0.12, 0.84±0.10, and 0.87±0.06, respectively, when compared with the observed ground truth. Considering only the regions without evidence of GA at baseline, predicted regions of future GA growth showed relatively high Dice indices of 0.72±0.18, 0.74±0.17, and 0.72±0.22, respectively. Predictions and actual values of GA growth rate and future GA involvement in the central fovea showed high correlations. CONCLUSIONS: Experimental results demonstrated the potential of our predictive model to predict future regions where GA is likely to grow and to identify the most discriminant early indicator (thickness loss of bands 11 through 14) of regions susceptible to GA growth.

Automated segmentation of optic disc in SD-OCT images and cup-to-disc ratios quantification by patch searching-based neural canal opening detection.

Glaucoma is one of the most common causes of blindness worldwide. Early detection of glaucoma is traditionally based on assessment of the cup-to-disc (C/D) ratio, an important indicator of structural changes to the optic nerve head. Here, we present an automated optic disc segmentation algorithm in 3-D spectral domain optical coherence tomography (SD-OCT) volumes to quantify this ratio. The proposed algorithm utilizes a two-stage strategy. First, it detects the neural canal opening (NCO) by finding the points with maximum curvature on the retinal pigment epithelium (RPE) boundary with a spatial correlation smoothness constraint on consecutive B-scans, and it approximately locates the coarse disc margin in the projection image using convex hull fitting. Then, a patch searching procedure using a probabilistic support vector machine (SVM) classifier finds the most likely patch with the NCO in its center in order to refine the segmentation result. Thus, a reference plane can be determined to calculate the C/D radio. Experimental results on 42 SD-OCT volumes from 17 glaucoma patients demonstrate that the proposed algorithm can achieve high segmentation accuracy and a low C/D ratio evaluation error. The unsigned border error for optic disc segmentation and the evaluation error for C/D ratio comparing with manual segmentation are 2.216 ± 1.406 pixels (0.067 ± 0.042 mm) and 0.045 ± 0.033, respectively.

Application of improved homogeneity similarity-based denoising in optical coherence tomography retinal images.

Image denoising is a fundamental preprocessing step of image processing in many applications developed for optical coherence tomography (OCT) retinal imaging--a high-resolution modality for evaluating disease in the eye. To make a homogeneity similarity-based image denoising method more suitable for OCT image removal, we improve it by considering the noise and retinal characteristics of OCT images in two respects: (1) median filtering preprocessing is used to make the noise distribution of OCT images more suitable for patch-based methods; (2) a rectangle neighborhood and region restriction are adopted to accommodate the horizontal stretching of retinal structures when observed in OCT images. As a performance measurement of the proposed technique, we tested the method on real and synthetic noisy retinal OCT images and compared the results with other well-known spatial denoising methods, including bilateral filtering, five partial differential equation (PDE)-based methods, and three patch-based methods. Our results indicate that our proposed method seems suitable for retinal OCT imaging denoising, and that, in general, patch-based methods can achieve better visual denoising results than point-based methods in this type of imaging, because the image patch can better represent the structured information in the images than a single pixel. However, the time complexity of the patch-based methods is substantially higher than that of the others.

An improved optical coherence tomography-derived fundus projection image for drusen visualization.

PURPOSE: To develop and evaluate an improved method of generating en face fundus images from three-dimensional optical coherence tomography images which enhances the visualization of drusen. METHODS: We describe a novel approach, the restricted summed-voxel projection (RSVP), to generate en face projection images of the retinal surface combined with an image processing method to enhance drusen visualization. The RSVP approach is an automated method that restricts the projection to the retinal pigment epithelium layer neighborhood. Additionally, drusen visualization is improved through an image processing technique that fills drusen with bright pixels. The choroid layer is also excluded when creating the RSVP to eliminate bright pixels beneath drusen that could be confused with drusen when geographic atrophy is present. The RSVP method was evaluated in 46 patients and 3-dimensional optical coherence tomography data sets were obtained from 8 patients, for which 2 readers independently identified drusen as the gold standard. The mean drusen overlap ratio was used as the metric to determine the accuracy of visualization of the RSVP method when compared with the conventional summed-voxel projection technique. RESULTS: Comparative results demonstrate that the RSVP method was more effective than the conventional summed-voxel projection in displaying drusen and retinal vessels, and was more useful in detecting drusen. The mean drusen overlap ratios based on the conventional summed-voxel projection method and the RSVP method were 2.1% and 89.3%, respectively. CONCLUSION: The RSVP method was more effective for drusen visualization than the conventional summed-voxel projection method, and it may be useful for macular assessment in patients with nonexudative age-related macular degeneration.

A false color fusion strategy for drusen and geographic atrophy visualization in optical coherence tomography images.

PURPOSE: To display drusen and geographic atrophy (GA) in a single projection image from three-dimensional spectral domain optical coherence tomography images based on a novel false color fusion strategy. METHODS: We present a false color fusion strategy to combine drusen and GA projection images. The drusen projection image is generated with a restricted summed-voxel projection (axial sum of the reflectivity values in a spectral domain optical coherence tomography cube, limited to the region where drusen is present). The GA projection image is generated by incorporating two GA characteristics: bright choroid and thin retina pigment epithelium. The false color fusion method was evaluated in 82 three-dimensional optical coherence tomography data sets obtained from 7 patients, for which 2 readers independently identified drusen and GA as the gold standard. The mean drusen and GA overlap ratio was used as the metric to determine accuracy of visualization of the proposed method when compared with the conventional summed-voxel projection, (axial sum of the reflectivity values in the complete spectral domain optical coherence tomography cube) technique and color fundus photographs. RESULTS: Comparative results demonstrate that the false color image is more effective in displaying drusen and GA than summed-voxel projection and CFP. The mean drusen/GA overlap ratios based on the conventional summed-voxel projection method, color fundus photographs, and the false color fusion method were 6.4%/100%, 64.1%/66.7%, and 85.6%/100%, respectively. CONCLUSION: The false color fusion method was more effective for simultaneous visualization of drusen and GA than the conventional summed-voxel projection method and color fundus photographs, and it seems promising as an alternative method for visualizing drusen and GA in the retinal fundus, which commonly occur together and can be confusing to differentiate without methods such as this proposed one.

Spectral-Domain and Swept-Source OCT Angiographic Scans Yield Similar Drusen Measurements When Processed with the Same Algorithm.

Purpose: An algorithm developed to obtain drusen area and volume measurements using swept-source OCT angiography (SS-OCTA) scans was tested on spectral-domain OCT angiography (SD-OCTA) scans. Design: Retrospective study. Participants: Forty pairs of scans from 27 eyes with intermediate age-related macular degeneration and drusen. Methods: Patients underwent both SD-OCTA and SS-OCTA imaging at the same visit using the 6 mm × 6 mm OCTA scan patterns. Using the same algorithm, we obtained drusen area and volume measurements within both 3 mm and 5 mm fovea-centered circles. Paired 2-sample t-tests were performed along with Pearson's correlation tests. Main Outcome Measures: Mean square root (sqrt) drusen area and cube root (cbrt) drusen volume within the 3 mm and 5 mm fovea-centered circles. Results: Mean sqrt drusen area values from SD-OCTA and SS-OCTA scans were 1.57 (standard deviation [SD] 0.57) mm and 1.49 (SD 0.58) mm in the 3 mm circle and 1.88 (SD 0.59) mm and 1.76 (SD 0.58) mm in the 5 mm circle, respectively. Mean cbrt drusen volume measurements were 0.54 (SD 0.19) mm and 0.51 (SD 0.20) mm in the 3 mm circle, and 0.60 (SD 0.17) mm and 0.57 (SD 0.17) mm in the 5 mm circle. Small differences in area and volume measurements were found (all P < 0.001); however, the correlations between the instruments were strong (all coefficients > 0.97; all P < 0.001). Conclusions: An algorithm originally developed for SS-OCTA scans performs well when used to obtain drusen volume and area measurements from SD-OCTA scans; thus, a separate SD-OCT structural scan is unnecessary to obtain measurements of drusen. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

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.

The Impact of Cataracts on the Measurement of Macular Choriocapillaris Flow Deficits Using Swept-Source OCT Angiography.

Purpose: The impact of cataracts on the measurement of macular choriocapillaris flow deficits (CC FDs) was assessed by comparing the quantitative results before and after cataract surgery using an image quality algorithm developed for swept-source optical coherence tomography angiography (SS-OCTA) scans and a validated strategy for quantifying the CC FDs. Methods: SS-OCTA image quality scores and CC FDs measurements within the fovea-centered 1-mm, 3-mm, and 5-mm diameter circles were compared before and after cataract surgery. CC FDs changes in a modified Early Treatment Diabetic Retinopathy Study (ETDRS) grid were further investigated. Results: Twenty-four eyes were studied. Overall image quality in all three circles was observed to improve significantly following the removal of cataracts (all P < 0.05). Although there was good repeatability in the measurements of CC FDs at both visits (intraclass correlation coefficients were over 0.95), significant decreases in CC FD measurements were observed after surgery within the 1-mm circle (P < 0.001) and the 3-mm circle (P = 0.011), but no changes were observed within the 5-mm circle (P = 0.509) or any of the quadrant sectors of the modified ETDRS grid (all P > 0.05). Conclusions: The presence of cataracts resulted in worse image quality and increased CC FD measurements within the fovea-centered 1-mm and 3-mm circles, with the 1-mm circle being impacted the most. Translational Relevance: The impaired detection of CC perfusion deficits within the central macula of cataract eyes needs to be appreciated when imaging the CC in phakic eyes, especially in clinical trials.

A Deep Learning Model for Automated Segmentation of Geographic Atrophy Imaged Using Swept-Source OCT.

PURPOSE: To present a deep learning algorithm for segmentation of geographic atrophy (GA) using en face swept-source OCT (SS-OCT) images that is accurate and reproducible for the assessment of GA growth over time. DESIGN: Retrospective review of images obtained as part of a prospective natural history study. SUBJECTS: Patients with GA (n = 90), patients with early or intermediate age-related macular degeneration (n = 32), and healthy controls (n = 16). METHODS: An automated algorithm using scan volume data to generate 3 image inputs characterizing the main OCT features of GA-hypertransmission in subretinal pigment epithelium (sub-RPE) slab, regions of RPE loss, and loss of retinal thickness-was trained using 126 images (93 with GA and 33 without GA, from the same number of eyes) using a fivefold cross-validation method and data augmentation techniques. It was tested in an independent set of one hundred eighty 6 × 6-mm2 macular SS-OCT scans consisting of 3 repeated scans of 30 eyes with GA at baseline and follow-up as well as 45 images obtained from 42 eyes without GA. MAIN OUTCOME MEASURES: The GA area, enlargement rate of GA area, square root of GA area, and square root of the enlargement rate of GA area measurements were calculated using the automated algorithm and compared with ground truth calculations performed by 2 manual graders. The repeatability of these measurements was determined using intraclass coefficients (ICCs). RESULTS: There were no significant differences in the GA areas, enlargement rates of GA area, square roots of GA area, and square roots of the enlargement rates of GA area between the graders and the automated algorithm. The algorithm showed high repeatability, with ICCs of 0.99 and 0.94 for the GA area measurements and the enlargement rates of GA area, respectively. The repeatability limit for the GA area measurements made by grader 1, grader 2, and the automated algorithm was 0.28, 0.33, and 0.92 mm2, respectively. CONCLUSIONS: When compared with manual methods, this proposed deep learning-based automated algorithm for GA segmentation using en face SS-OCT images was able to accurately delineate GA and produce reproducible measurements of the enlargement rates of GA.

Choroidal Changes After Anti-VEGF Therapy in AMD Eyes With Different Types of Macular Neovascularization Using Swept-Source OCT Angiography.

Purpose: Choroidal changes before and after anti-VEGF therapy were investigated in eyes with exudative AMD to determine if there was a difference between eyes with macular neovascularization (MNV) that arises from the choroid (type 1 or 2) versus the retinal circulation (type 3). Methods: Patients with treatment-naïve AMD were imaged with swept-source optical coherence tomography angiography using a 12 × 12-mm scan pattern. The mean choroidal thickness and choroidal vascularity index (CVI) were measured within 5-mm and 11-mm fovea-centered circles before, at the onset of, and after anti-VEGF therapy. Results: Forty-one eyes of 37 patients were included; 24 eyes with type 1 MNV, 4 eyes with type 2 MNV, and 13 eyes with type 3 MNV. Within the 5-mm and 11-mm circles, the mean choroidal thickness and CVI measurements increased from pretreatment to the onset of exudation (P ≤ 0.03). The mean choroidal thickness and CVI measurements decreased from the onset of exudation to after treatment (P < 0.001). No significant changes in mean choroidal thickness or CVI were observed when comparing measurements before or after treatment (P ≥ 0.38). No significant differences in mean choroidal thickness or CVI measurements were observed between eyes with type 1 or 2 MNV and type 3 MNV. Conclusions: In treatment-naïve AMD eyes with MNV, the choroidal thickness and vascularity increased at the onset of exudation and then decreased after anti-VEGF therapy. This finding suggests that these choroidal changes develop in response to the proangiogenic milieu before treatment and in response to treatment, regardless of the site of origin for the MNV.

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.

Decreased Central Macular Choriocapillaris Perfusion Correlates With Increased Low Luminance Visual Acuity Deficits.

PURPOSE: Correlations between low luminance visual acuity deficits (LLVADs) and central choriocapillaris perfusion deficits were investigated to help explain how increases in LLVAD scores at baseline predict annual growth rates of geographic atrophy (GA). DESIGN: Prospective cross-sectional study. METHODS: Photopic luminance best-corrected visual acuity (PL-BCVA) and low luminance BCVA (LL-BCVA) were measured using the Early Treatment Diabetic Retinopathy Study chart. LL-BCVA was measured using a 2.0-log unit neutral density filter. LLVADs were calculated as the difference between PL-BCVA and LL-BCVA. Within a fovea-centered 1-mm circle, the percentage of choriocapillaris flow deficits (CC FD%), drusen volume, optical attenuation coefficient (OAC) elevation volume, and outer retinal layer (ORL) thickness were assessed. RESULTS: In all 90 eyes (30 normal eyes; 31 drusen-only eyes; 29 non-foveal GA eyes), significant correlations were found between the central CC FD% and PL-BCVA (r = -0.393, P < .001), LL-BCVA (r = -0.534, P < .001), and the LLVAD (r = 0.439, P < .001). Central cube root (cubrt) drusen volume, cubrt OAC elevation volume, and ORL thickness were correlated with PL-BCVA, LL-BCVA, and LLVADs (all P < .05). Stepwise regression models showed that central cubrt OAC elevation volume and ORL thickness were associated with PL-BCVA (R2 = 0.24, P < .05); central CC FD%, cubrt OAC elevation volume, and ORL thickness were associated with LL-BCVA (R2 = 0.44, P < .01); and central CC FD% and ORL thickness were associated with LLVAD (R2 = 0.24, P < .01). CONCLUSIONS: The significant correlations between central CC FD% and LLVAD support the hypothesis that the ability of LLVAD to predict the growth of GA is mediated through a decrease in macular choriocapillaris perfusion.

TOPOGRAPHIC OPTICAL COHERENCE TOMOGRAPHY SEGMENTATION SHOWS LIMITED ELLIPSOID ZONE RECOVERY IN MILD HYDROXYCHLOROQUINE RETINOPATHY.

PURPOSE: Optical coherence tomography (OCT) cross-sections have shown limited ellipsoid zone (EZ) improvement in mild hydroxychloroquine (HCQ) retinopathy within a few years after drug cessation. However, the extent, functional significance, and stability of such changes over time remain unclear. METHODS: We created en face EZ maps using automated pixel-by-pixel segmentation for four patients with early-moderate HCQ toxicity followed for 6-8 years after drug cessation. These maps were compared with OCT cross-sections, fundus autofluorescence, and automated 10-2 visual fields. RESULTS: One patient had no EZ line loss; one had stable EZ loss throughout follow-up; two showed 30 to 40% reduction in the area of loss, largely in the first 2 years. This limited recovery mostly occurred in regions where the EZ line was only thinned or fragmented; other similar areas did not improve. Fundus autofluorescence hyperfluorescence and visual fields did not show consistent correlation with topography. CONCLUSION: Anatomic EZ recovery, when present, was restricted to regions of mild damage and did not correlate with fundus autofluorescence or improvement in visual fields. Topographic mapping seemed no more sensitive locally than cross-sectional OCT but may aid detection and longitudinal follow-up of toxicity by showing early damage or changes in the macula that could be missed with individual cross-sections.

Does the Outer Retinal Thickness Around Geographic Atrophy Represent Another Clinical Biomarker for Predicting Growth?

PURPOSE: To determine whether the outer retinal layer (ORL) thickness around geographic atrophy (GA) could serve as a clinical biomarker to predict the annual enlargement rate (ER) of GA. DESIGN: Retrospective analysis of a prospective, observational case series. METHODS: Eyes with GA were imaged with a swept-source OCT 6 × 6 mm scan pattern. GA lesions were measured from customized en face OCT images and the annual ERs were calculated. The ORL was defined and segmented from the inner boundary of outer plexiform layer (OPL) to the inner boundary of retinal pigment epithelium (RPE) layer. The ORL thickness was measured at different subregions around GA. RESULTS: A total of 38 eyes from 27 participants were included. The same eyes were used for the choriocapillaris (CC) flow deficit (FD) analysis and the RPE to the Bruch membrane (RPE-BM) distance measurements. A negative correlation was observed between the ORL thickness and the GA growth. The ORL thickness in a 300-µm rim around GA showed the strongest correlation with the GA growth (r = -0.457, P = .004). No correlations were found between the ORL thickness and the CC FDs; however, a significant correlation was found between the ORL thickness and the RPE-BM distances around GA (r = -0.398, P = .013). CONCLUSIONS: ORL thickness showed a significant negative correlation with annual GA growth, but also showed a significant correlation with the RPE-BM distances, suggesting that they were dependently correlated with GA growth. This finding suggests that the loss of photoreceptors was associated with the formation of basal laminar deposits around GA.

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.

Automatic geographic atrophy segmentation using optical attenuation in OCT scans with deep learning.

A deep learning algorithm was developed to automatically identify, segment, and quantify geographic atrophy (GA) based on optical attenuation coefficients (OACs) calculated from optical coherence tomography (OCT) datasets. Normal eyes and eyes with GA secondary to age-related macular degeneration were imaged with swept-source OCT using 6 × 6 mm scanning patterns. OACs calculated from OCT scans were used to generate customized composite en face OAC images. GA lesions were identified and measured using customized en face sub-retinal pigment epithelium (subRPE) OCT images. Two deep learning models with the same U-Net architecture were trained using OAC images and subRPE OCT images. Model performance was evaluated using DICE similarity coefficients (DSCs). The GA areas were calculated and compared with manual segmentations using Pearson's correlation and Bland-Altman plots. In total, 80 GA eyes and 60 normal eyes were included in this study, out of which, 16 GA eyes and 12 normal eyes were used to test the models. Both models identified GA with 100% sensitivity and specificity on the subject level. With the GA eyes, the model trained with OAC images achieved significantly higher DSCs, stronger correlation to manual results and smaller mean bias than the model trained with subRPE OCT images (0.940 ± 0.032 vs 0.889 ± 0.056, p = 0.03, paired t-test, r = 0.995 vs r = 0.959, mean bias = 0.011 mm vs mean bias = 0.117 mm). In summary, the proposed deep learning model using composite OAC images effectively and accurately identified, segmented, and quantified GA using OCT scans.

SEQUENTIAL RETINAL THICKNESS ANALYSIS SHOWS HYDROXYCHLOROQUINE DAMAGE BEFORE OTHER SCREENING TECHNIQUES.

PURPOSE: We sought to determine the earliest diagnostic signs of hydroxychloroquine retinopathy up to the point of clinical recognition. METHODS: Retrospective series of 6 patients (5 parafoveal disease; 1 pericentral disease) with at least 3 examinations over 3.5 years or more preceding diagnosis of HCQ retinopathy. Spectral domain optical coherence tomography (sdOCT) cross-sections, fundus autofluorescence (FAF) and visual fields were generated clinically. Stored sdOCT data were re-examined later to generate topographic ellipsoid zone (EZ) maps, minimum intensity (MI) analysis and sequential plots of regional retinal thickness. Retrospective series of six patients (5 parafoveal disease; one pericentral disease) with at least three examinations over 3.5 years or more preceding diagnosis of hydroxychloroquine retinopathy. RESULTS: Spectral domain optical coherence tomography cross-sections and fields showed similar sensitivity; fundus autofluorescence was not helpful. In parafoveal cases, EZ topography and minimum intensity analysis were no more reliable. Sequential thickness plots from four parafoveal cases showed dramatic retinal thinning across the posterior pole beginning 4 years to 5 years before clinical diagnosis, with parafoveal regions thinning even faster. The pericentral case showed thinning only outside the central macula. Peripheral EZ loss was more dramatic with EZ topography than sdOCT cross-sections. CONCLUSION: Sequential retinal thickness plots reveal definitive thinning years before current diagnostic procedures. We hope that OCT manufacturers will develop software to display such measurements. Ellipsoid zone topography was not more sensitive than sdOCT cross-sections, but important for recognizing pericentral disease.

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.