Publications by authors named "Thomas S Hwang"

63 Publications

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Ophthalmology 2021 May 10. Epub 2021 May 10.

National Eye Institute| National Institutes of Health, Bethesda, Maryland.

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http://dx.doi.org/10.1016/j.ophtha.2021.04.011DOI Listing
May 2021

Comparison of Central Macular Fluid Volume With Central Subfield Thickness in Patients With Diabetic Macular Edema Using Optical Coherence Tomography Angiography.

JAMA Ophthalmol 2021 May 13. Epub 2021 May 13.

Casey Eye Institute, Oregon Health & Science University, Portland.

Importance: Diabetic macular edema (DME) is the predominant cause of visual impairment in patients with type 1 or 2 diabetes. Automated fluid volume measurements using optical coherence tomography (OCT) may improve the diagnostic accuracy of DME screening.

Objective: To assess the diagnostic accuracy of an automated central macular fluid volume (CMFV) quantification using OCT for DME.

Design, Setting, And Participants: A cross-sectional observational study was conducted at a tertiary academic center among 215 patients with diabetes (1 eye each) enrolled from January 26, 2015, to December 23, 2019. All participants underwent comprehensive examinations, 6 × 6-mm macular structural OCT horizontal raster scans, and 6 × 6-mm macular OCT angiography volumetric scans. From January 1 to March 30, 2020, 2 retinal specialists reviewed the structural OCT scans independently and diagnosed DME if intraretinal or subretinal fluid was present. Diabetic macular edema was considered center involved if fluid was present within the central fovea (central 1-mm circle). A third retinal specialist arbitrated any discrepancy. The mean central subfield thickness (CST) within the central fovea was measured on structural OCT horizontal raster scans. A deep learning algorithm automatically quantified fluid volumes on 6 × 6-mm OCT angiography volumetric scans and within the central foveas (CMFV).

Main Outcomes And Measures: The area under the receiver operating characteristic curve (AUROC) and the sensitivity and specificity of CST and CMFV for DME diagnosis.

Results: We enrolled 1 eye each of 215 patients with diabetes (117 women [54.4%]; mean [SD] age, 59.6 [12.4] years). Diabetic macular edema was present in 136 eyes; 93 cases of DME were center involved. The AUROC of CMFV for diagnosis of center-involved DME (0.907 [95% CI, 0.861-0.954]) was greater than the AUROC of CST (0.832 [95% CI, 0.775-0.889]; P = .02). With the specificity set at 95%, the sensitivity of CMFV for detection of center-involved DME (78.5% [95% CI, 68.8%-86.3%]) was higher than that of CST (53.8% [95% CI, 43.1%-64.2%]; P = .002). Center-involved DME cases not detected by CST but detected by CMFV were associated with a thinner CST (290.8 μm [95% CI, 282.3-299.3 μm] vs 369.4 μm [95% CI, 347.1-391.7 μm]; P < .001), higher proportion of previous macular laser treatment (11 of 28 [39.3%; 95% CI, 21.5%-59.4%] vs 12 of 65 [18.5%; 95% CI, 9.9%-30.0%]; P = .03), and female sex (20 of 28 [71.4%; 95% CI, 51.3%-86.8%] vs 31 of 65 [47.7%; 95% CI, 35.1%-60.5%]; P = .04).

Conclusions And Relevance: These findings suggest that an automated CMFV is a more accurate diagnostic biomarker than CST for DME and may improve screening for DME.
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http://dx.doi.org/10.1001/jamaophthalmol.2021.1275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120439PMC
May 2021

Artificial intelligence in OCT angiography.

Prog Retin Eye Res 2021 Mar 22:100965. Epub 2021 Mar 22.

Casey Eye Institute, Oregon Health & Science University, Portland, OR, 97239, USA; Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR, 97239, USA. Electronic address:

Optical coherence tomographic angiography (OCTA) is a non-invasive imaging modality that provides three-dimensional, information-rich vascular images. With numerous studies demonstrating unique capabilities in biomarker quantification, diagnosis, and monitoring, OCTA technology has seen rapid adoption in research and clinical settings. The value of OCTA imaging is significantly enhanced by image analysis tools that provide rapid and accurate quantification of vascular features and pathology. Today, the most powerful image analysis methods are based on artificial intelligence (AI). While AI encompasses a large variety of techniques, machine-learning-based, and especially deep-learning-based, image analysis provides accurate measurements in a variety of contexts, including different diseases and regions of the eye. Here, we discuss the principles of both OCTA and AI that make their combination capable of answering new questions. We also review contemporary applications of AI in OCTA, which include accurate detection of pathologies such as choroidal neovascularization, precise quantification of retinal perfusion, and reliable disease diagnosis.
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http://dx.doi.org/10.1016/j.preteyeres.2021.100965DOI Listing
March 2021

Plexus-specific retinal capillary avascular area in exudative age-related macular degeneration with projection-resolved OCT angiography.

Br J Ophthalmol 2020 Dec 22. Epub 2020 Dec 22.

Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA

Objective: To detect the plexus-specific retinal capillary avascular area in exudative age-related macular degeneration (EAMD) with projection-resolved optical coherence tomography angiography (PR-OCTA).

Methods And Analysis: In this prospective cross-sectional single centre study, eyes with treatment-naïve EAMD underwent macular 3×3 mm OCTA with AngioVue system. OCTA scans were analysed and processed including three-dimensional projection artefact removal, retinal layer semi-automated segmentation and en face angiogram generation. Automated quantification of extrafoveal (excluding the central 1 mm circle) avascular area (EAA) were calculated on projection-resolved superficial vascular complex (SVC), intermediate capillary plexus (ICP) and deep capillary plexus (DCP), respectively.

Results: Nineteen eyes with EAMD and 19 age-matched healthy control eyes were included. There was no significant difference between the EAMD and control eyes in terms of age, sex, axial length and mean ocular perfusion pressure (all p>0.05). Compared with control eyes, EAMD eyes had significantly larger EAA in SVC (median 0.125 vs 0.059 mm, p=0.006), ICP (0.016 vs 0.000 mm, p=0.004) and DCP (0.033 vs 0.000 mm, p<0.001).

Conclusion: PR-OCTA showed that EAMD is associated with focal avascular area in all the three retinal vascular plexuses.
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http://dx.doi.org/10.1136/bjophthalmol-2020-317562DOI Listing
December 2020

Segmenting OCT for detecting drug efficacy in CRAO.

PLoS One 2020 11;15(12):e0242920. Epub 2020 Dec 11.

Senju Laboratory of Ocular Sciences, Portland, OR, United States of America.

Purpose: Thinning of the inner layers of the retina occurs in patients with central retinal artery occlusion (CRAO). The mechanism for such thinning may be partially due to proteolysis by a calcium-activated protease called calpain. Calpain inhibitor SNJ-1945 ameliorated the proteolysis in a past series of model experiments. The purposes of the present retrospective study were to: 1) use segmentation analysis of optical coherence tomography (OCT) images to mathematically model the loss of specific retinal layers in CRAO patients, and 2) predict the number of patients and days of observation needed for clinical trials of inhibitors against CRAO.

Methods: A retrospective case control study was conducted by computer-aided search for CRAO (ICD10 H43.1) with at least one OCT procedure (CPT: 92134) in the OHSU Epic patient data base.

Results: After initial swelling, thinning of the inner retinal layers, especially the ganglion cell (GCL) layer followed exponential decay curves. Using sample size statistics and GCL thickness as a marker in a 30-day clinical trial, 19 eyes/group could theoretically detect a 20% beneficial effect of an inhibitor against CRAO. Other markers, such as the whole retinal thickness and combined inner layers could also be used as less-specific markers.

Conclusions: Using thickness changes in the GCL layer to monitor the efficacy of potential inhibitors against CRAO is practical in human trials requiring a reasonable number of patients and relatively short trial period.

Translational Relevance: Measurement of GCL thickness would be a useful indicator of CRAO progression in a clinical trial of putative inhibitors.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242920PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732080PMC
January 2021

Automated Segmentation of Retinal Fluid Volumes From Structural and Angiographic Optical Coherence Tomography Using Deep Learning.

Transl Vis Sci Technol 2020 10 8;9(2):54. Epub 2020 Oct 8.

Casey Eye Institute, Oregon Health & Science University, Portland, OR, USA.

Purpose: We proposed a deep convolutional neural network (CNN), named Retinal Fluid Segmentation Network (ReF-Net), to segment retinal fluid in diabetic macular edema (DME) in optical coherence tomography (OCT) volumes.

Methods: The 3- × 3-mm OCT scans were acquired on one eye by a 70-kHz OCT commercial AngioVue system (RTVue-XR; Optovue, Inc., Fremont, CA, USA) from 51 participants in a clinical diabetic retinopathy (DR) study (45 with retinal edema and six healthy controls, age 61.3 ± 10.1 (mean ± SD), 33% female, and all DR cases were diagnosed as severe NPDR or PDR). A CNN with U-Net-like architecture was constructed to detect and segment the retinal fluid. Cross-sectional OCT and angiography (OCTA) scans were used for training and testing ReF-Net. The effect of including OCTA data for retinal fluid segmentation was investigated in this study. Volumetric retinal fluid can be constructed using the output of ReF-Net. Area-under-receiver-operating-characteristic-curve, intersection-over-union (IoU), and F1-score were calculated to evaluate the performance of ReF-Net.

Results: ReF-Net shows high accuracy (F1 = 0.864 ± 0.084) in retinal fluid segmentation. The performance can be further improved (F1 = 0.892 ± 0.038) by including information from both OCTA and structural OCT. ReF-Net also shows strong robustness to shadow artifacts. Volumetric retinal fluid can provide more comprehensive information than the two-dimensional (2D) area, whether cross-sectional or en face projections.

Conclusions: A deep-learning-based method can accurately segment retinal fluid volumetrically on OCT/OCTA scans with strong robustness to shadow artifacts. OCTA data can improve retinal fluid segmentation. Volumetric representations of retinal fluid are superior to 2D projections.

Translational Relevance: Using a deep learning method to segment retinal fluid volumetrically has the potential to improve the diagnostic accuracy of diabetic macular edema by OCT systems.
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http://dx.doi.org/10.1167/tvst.9.2.54DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7552937PMC
October 2020

Reconstruction of high-resolution 6×6-mm OCT angiograms using deep learning.

Biomed Opt Express 2020 Jul 8;11(7):3585-3600. Epub 2020 Jun 8.

Casey Eye Institute, Oregon Health & Science University, Portland, OR 97239, USA.

Typical optical coherence tomographic angiography (OCTA) acquisition areas on commercial devices are 3×3- or 6×6-mm. Compared to 3×3-mm angiograms with proper sampling density, 6×6-mm angiograms have significantly lower scan quality, with reduced signal-to-noise ratio and worse shadow artifacts due to undersampling. Here, we propose a deep-learning-based high-resolution angiogram reconstruction network (HARNet) to generate enhanced 6×6-mm superficial vascular complex (SVC) angiograms. The network was trained on data from 3×3-mm and 6×6-mm angiograms from the same eyes. The reconstructed 6×6-mm angiograms have significantly lower noise intensity, stronger contrast and better vascular connectivity than the original images. The algorithm did not generate false flow signal at the noise level presented by the original angiograms. The image enhancement produced by our algorithm may improve biomarker measurements and qualitative clinical assessment of 6×6-mm OCTA.
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http://dx.doi.org/10.1364/BOE.394301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510902PMC
July 2020

DcardNet: Diabetic Retinopathy Classification at Multiple Levels Based on Structural and Angiographic Optical Coherence Tomography.

IEEE Trans Biomed Eng 2021 Jun 21;68(6):1859-1870. Epub 2021 May 21.

Objective: Optical coherence tomography (OCT) and its angiography (OCTA) have several advantages for the early detection and diagnosis of diabetic retinopathy (DR). However, automated, complete DR classification frameworks based on both OCT and OCTA data have not been proposed. In this study, a convolutional neural network (CNN) based method is proposed to fulfill a DR classification framework using en face OCT and OCTA.

Methods: A densely and continuously connected neural network with adaptive rate dropout (DcardNet) is designed for the DR classification. In addition, adaptive label smoothing was proposed and used to suppress overfitting. Three separate classification levels are generated for each case based on the International Clinical Diabetic Retinopathy scale. At the highest level the network classifies scans as referable or non-referable for DR. The second level classifies the eye as non-DR, non-proliferative DR (NPDR), or proliferative DR (PDR). The last level classifies the case as no DR, mild and moderate NPDR, severe NPDR, and PDR.

Results: We used 10-fold cross-validation with 10% of the data to assess the network's performance. The overall classification accuracies of the three levels were 95.7%, 85.0%, and 71.0% respectively.

Conclusion/significance: A reliable, sensitive and specific automated classification framework for referral to an ophthalmologist can be a key technology for reducing vision loss related to DR.
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http://dx.doi.org/10.1109/TBME.2020.3027231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191487PMC
June 2021

Plexus-specific retinal vascular anatomy and pathologies as seen by projection-resolved optical coherence tomographic angiography.

Prog Retin Eye Res 2021 01 24;80:100878. Epub 2020 Jul 24.

Casey Eye Institute, Oregon Health & Science University, Portland, OR, 97239, USA. Electronic address:

Optical coherence tomographic angiography (OCTA) is a novel technology capable of imaging retinal vasculature three-dimensionally at capillary scale without the need to inject any extrinsic dye contrast. However, projection artifacts cause superficial retinal vascular patterns to be duplicated in deeper layers, thus interfering with the clean visualization of some retinal plexuses and vascular pathologies. Projection-resolved OCTA (PR-OCTA) uses post-processing algorithms to reduce projection artifacts. With PR-OCTA, it is now possible to resolve up to 4 distinct retinal vascular plexuses in the living human eye. The technology also allows us to detect and distinguish between various retinal and optic nerve diseases. For example, optic nerve diseases such as glaucoma primarily reduces the capillary density in the superficial vascular complex, which comprises the nerve fiber layer plexus and the ganglion cell layer plexus. Outer retinal diseases such as retinitis pigmentosa primarily reduce the capillary density in the deep vascular complex, which comprises the intermediate capillary plexus and the deep capillary plexus. Retinal vascular diseases such as diabetic retinopathy and vein occlusion affect all plexuses, but with different patterns of capillary loss and vascular malformations. PR-OCTA is also useful in distinguishing various types of choroidal neovascularization and monitoring their response to anti-angiogenic medications. In retinal angiomatous proliferation and macular telangiectasia type 2, PR-OCTA can trace the pathologic vascular extension into deeper layers as the disease progress through stages. Plexus-specific visualization and measurement of retinal vascular changes are improving our ability to diagnose, stage, monitor, and assess treatment response in a wide variety of optic nerve and retinal diseases. These applications will be further enhanced with the continuing improvement of the speed and resolution of the OCT platforms, as well as the development of software algorithms to reduce artifacts, improve image quality, and make quantitative measurements.
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http://dx.doi.org/10.1016/j.preteyeres.2020.100878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855241PMC
January 2021

High-resolution wide-field OCT angiography with a self-navigation method to correct microsaccades and blinks.

Biomed Opt Express 2020 Jun 21;11(6):3234-3245. Epub 2020 May 21.

Casey Eye Institute, Oregon Health and Science University, Portland, Oregon 97239, USA.

In this study, we demonstrate a novel self-navigated motion correction method that suppresses eye motion and blinking artifacts on wide-field optical coherence tomographic angiography (OCTA) without requiring any hardware modification. Highly efficient GPU-based, real-time OCTA image acquisition and processing software was developed to detect eye motion artifacts. The algorithm includes an instantaneous motion index that evaluates the strength of motion artifact on OCTA images. Areas with suprathreshold motion and eye blinking artifacts are automatically rescanned in real-time. Both healthy eyes and eyes with diabetic retinopathy were imaged, and the self-navigated motion correction performance was demonstrated.
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http://dx.doi.org/10.1364/BOE.390430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7316026PMC
June 2020

Optical Coherence Tomography Angiography Avascular Area Association With 1-Year Treatment Requirement and Disease Progression in Diabetic Retinopathy.

Am J Ophthalmol 2020 09 29;217:268-277. Epub 2020 Apr 29.

Casey Eye Institute, Oregon Health and Science University, Portland, Oregon, USA. Electronic address:

Purpose: To assess the association between optical coherence tomography angiography (OCTA)-quantified avascular areas (AAs) and diabetic retinopathy (DR) severity, progression, and treatment requirement in the following year.

Design: Prospective cohort study.

Methods: We recruited patients with diabetes from a tertiary academic retina practice and obtained 3-mm × 3-mm macular OCTA scans with the AngioVue system and standard 7-field color photographs at baseline and at a 1-year follow-up visit. A masked grader determined the severity of DR from the color photographs using the Early Treatment of Diabetic Retinopathy scale. A custom algorithm detected extrafoveal AA (EAA) excluding the central 1-mm circle in projection-resolved superficial vascular complex (SVC), intermediate capillary plexus (ICP), and deep capillary plexus (DCP).

Results: Of 138 patients, 92 (41 men, ranging in age from 26-84 years [mean 59.4 years]) completed 1 year of follow-up. At baseline, EAAs for SVC, ICP, and DCP were all significantly correlated with retinopathy severity (P < .0001). DCP EAA was significantly associated with worse visual acuity (r = -0.24, P = .02), but SVC and ICP EAA were not. At 1 year, 11 eyes progressed in severity by at least 1 step. Multivariate logistic regression analysis demonstrated the progression was significantly associated with baseline SVC EAA (odds ratio = 8.73, P = .04). During the follow-up period, 33 eyes underwent treatment. Multivariate analysis showed that treatment requirement was significantly associated with baseline DCP EAA (odds ratio = 3.39, P = .002). No baseline metric was associated with vision loss at 1 year.

Conclusions: EAAs detected by OCTA in diabetic eyes are significantly associated with baseline DR severity, disease progression, and treatment requirement over 1 year.
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http://dx.doi.org/10.1016/j.ajo.2020.04.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492451PMC
September 2020

Robust non-perfusion area detection in three retinal plexuses using convolutional neural network in OCT angiography.

Biomed Opt Express 2020 Jan 18;11(1):330-345. Epub 2019 Dec 18.

Casey Eye Institute, Oregon Health & Science University, Portland, OR 97239, USA.

Non-perfusion area (NPA) is a quantitative biomarker useful for characterizing ischemia in diabetic retinopathy (DR). Projection-resolved optical coherence tomographic angiography (PR-OCTA) allows visualization of retinal capillaries and quantify NPA in individual plexuses. However, poor scan quality can make current NPA detection algorithms unreliable and inaccurate. In this work, we present a robust NPA detection algorithm using convolutional neural network (CNN). By merging information from OCT angiograms and OCT reflectance images, the CNN could exclude signal reduction and motion artifacts and detect the avascular features from local to global with the resolution preserved. Across a wide range of signal strength indices, and on both healthy and DR eyes, the algorithm achieved high accuracy and repeatability.
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http://dx.doi.org/10.1364/BOE.11.000330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6968759PMC
January 2020

Detection of Reduced Retinal Vessel Density in Eyes with Geographic Atrophy Secondary to Age-Related Macular Degeneration Using Projection-Resolved Optical Coherence Tomography Angiography.

Am J Ophthalmol 2020 01 14;209:206-212. Epub 2019 Sep 14.

Casey Eye Institute, Oregon Health and Science University, Portland, Oregon, USA. Electronic address:

Purpose: To compare retinal vessel density in eyes with geographic atrophy (GA) secondary to age-related macular degeneration (AMD) to age-matched healthy eyes by using projection-resolved optical coherence tomography angiography (PR-OCTA).

Design: Prospective cross-sectional study.

Methods: Study participants underwent macular 3- × 3-mm OCTA scans with spectral domain OCTA. Reflectance-compensated retinal vessel densities were calculated on projection-resolved superficial vascular complex (SVC), intermediate capillary plexus (ICP), and deep capillary plexus (DCP). Quantitative analysis using normalized deviation compared the retinal vessel density in GA regions, 500-μm GA rim regions, and non-GA regions to similar macular locations in control eyes.

Results: Ten eyes with GA and 10 control eyes were studied. Eyes with GA had significantly lower vessel density in the SVC (54.8 ± 2.4% vs. 60.8 ± 3.1%; P < 0.001), ICP (34.0 ± 1.5% vs. 37.3 ± 1.7%; P = 0.003) and DCP (24.4 ± 2.3% vs. 28.0 ± 2.3%; P < 0.001) than control eyes. Retinal vessel density within the GA region decreased significantly in SVC, ICP, and DCP. Retinal vessel density in the GA rim region decreased in SVC and ICP but not in DCP. The non-GA region did not significantly deviate from normal controls. Eyes with GA had significantly reduced photoreceptor layer thickness; but similar nerve fiber layer, ganglion cell complex, inner nuclear layer, and outer plexiform layer thickness.

Conclusions: Eyes with GA have reduced retinal vessel density in SVC, ICP, and DCP compared to those in controls. Loss is greatest within regions of GA. Vessel density may be more sensitive than retinal layer thickness measurement in the detection of inner retinal change in eyes with GA.
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http://dx.doi.org/10.1016/j.ajo.2019.09.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6911625PMC
January 2020

Phenotypic Spectrum of Pentosan Polysulfate Sodium-Associated Maculopathy: A Multicenter Study.

JAMA Ophthalmol 2019 Nov;137(11):1275-1282

Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia.

Importance: A unique pigmentary maculopathy was recently described in 6 patients with long-term exposure to pentosan polysulfate sodium (PPS), a long-standing oral therapy for interstitial cystitis.

Objective: To characterize the exposure characteristics and clinical manifestations of PPS-associated maculopathy.

Design, Setting, And Participants: In this multi-institutional case series, medical records of patients who exhibited the characteristic maculopathy in the setting of prior PPS exposure were retrospectively reviewed. Data were collected from August 1, 2012, to October 1, 2018, and data were analyzed from October 2018 to January 2019.

Main Outcomes And Measures: Drug exposure, visual acuity, and retinal imaging characteristics.

Results: Of the 35 included patients (70 eyes), 34 (97%) were female, and the median (range) age was 60 (37-79) years. The median (range) duration of PPS intake was 15 (3-22) years, and the median (range) cumulative exposure was 1.61 (0.44-4.31) kg. The leading visual symptoms were metamorphopsia, blurred vision, and prolonged dark adaptation. Median (range) logMAR visual acuity of all eyes was 0.10 (-0.12 to 1.18). Fundus examination often revealed hyperpigmented macular spots (34 of 64 eyes [53%]) with interspersed pale-yellow deposits, although less commonly in eyes that exhibited retinal pigment epithelial atrophy (6 of 26 eyes [23%]; P < .001). Optical coherence tomography showed foci of retinal pigment epithelium elevation or thickening associated with hyperreflectance on near-infrared reflectance imaging. Fundus autofluorescence imaging typically revealed a symmetric, confluent pattern of hyperautofluorescent and hypoautofluorescent spots that involved the fovea in all eyes and extended to the retinal periphery in 24 eyes (36%). Longitudinal evaluation demonstrated dynamic changes in pigmentary abnormalities.

Conclusions And Relevance: These findings suggest that PPS-associated maculopathy is a vision-threatening condition that can manifest in the setting of long-term exposure to the drug. Multimodal imaging posits a distinctive clinical phenotype, characterized in this cohort by dynamic alterations within the retinal pigment epithelium and at the retinal pigment epithelium-photoreceptor interface. Ongoing work might explore causality and direct screening guidelines.
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http://dx.doi.org/10.1001/jamaophthalmol.2019.3392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6735406PMC
November 2019

Three-dimensional structural and angiographic evaluation of foveal ischemia in diabetic retinopathy: method and validation.

Biomed Opt Express 2019 Jul 24;10(7):3522-3532. Epub 2019 Jun 24.

Casey Eye Institute, Oregon Health & Science University, Portland, OR, 97239, USA.

Optical coherence tomography angiography (OCTA) allows us to noninvasively investigate foveal ischemia, a key feature of diabetic retinopathy (DR). However, the sizes of the foveal avascular zone (FAZ) have a significant variation in normal population, preventing the objective assessment of pathological enlargement of FAZ due to capillary dropout. Based on the relationship between FAZ and ganglion cell complex (GCC) thickness in normal eyes, we defined a theoretical baseline FAZ (tbFAZ) on structural OCT and measured 2D and 3D vessel density in its vicinity on the simultaneously acquired OCTA in normal and diabetic eyes. We found that the structure-based tbFAZ was a reliable reference to identify foveal ischemia and that the 3D vessel density demonstrated ischemia more effectively than the 2D method. The proposed 3D para-FAZ vessel density correlates well with DR severity and potentially is a useful diagnostic biomarker, especially in the early stages of DR.
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http://dx.doi.org/10.1364/BOE.10.003522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6640826PMC
July 2019

Development and validation of a deep learning algorithm for distinguishing the nonperfusion area from signal reduction artifacts on OCT angiography.

Biomed Opt Express 2019 Jul 12;10(7):3257-3268. Epub 2019 Jun 12.

Casey Eye Institute, Oregon Health & Science University, Portland, OR 97239, USA.

The capillary nonperfusion area (NPA) is a key quantifiable biomarker in the evaluation of diabetic retinopathy (DR) using optical coherence tomography angiography (OCTA). However, signal reduction artifacts caused by vitreous floaters, pupil vignetting, or defocus present significant obstacles to accurate quantification. We have developed a convolutional neural network, MEDnet-V2, to distinguish NPA from signal reduction artifacts in 6×6 mm OCTA. The network achieves strong specificity and sensitivity for NPA detection across a wide range of DR severity and scan quality.
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http://dx.doi.org/10.1364/BOE.10.003257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6640834PMC
July 2019

Detection of Nonexudative Choroidal Neovascularization and Progression to Exudative Choroidal Neovascularization Using OCT Angiography.

Ophthalmol Retina 2019 08 21;3(8):629-636. Epub 2019 Mar 21.

Casey Eye Institute, Oregon Health & Science University, Portland, Oregon.

Purpose: To detect nonexudative choroidal neovascularization (CNV) in age-related macular degeneration (AMD) with OCT angiography (OCTA) and determine the risk of exudative CNV developing compared with eyes without nonexudative CNV.

Design: Prospective, longitudinal, observational study.

Participants: Consecutive patients with drusen and pigmentary changes in the study eye and exudative neovascular AMD in the fellow eye.

Methods: In this prospective observational study, participants underwent spectral-domain OCTA (AngioVue; Optovue, Inc, Fremont, CA), clinical examination, and structural OCT at baseline and 6-month intervals for 2 years. OCT angiography images were exported for custom processing to remove projection artifact and calculate CNV vessel area.

Main Outcome Measures: Rate of developing exudation in eyes with and without nonexudative CNV as detected by OCTA on regular follow-up.

Results: Sixty-three study participants were followed up every 6 months and 48 completed the 2-year study. Mean age was 78 years and 60.3% were female. On the baseline visit, 5 eyes (7.9%) were found to have nonexudative CNV by OCTA, and 3 of them demonstrated exudation. Of 58 eyes with a normal OCTA on baseline visit, 5 eyes developed nonexudative CNV during a follow-up visit. All 5 of these nonexudative CNV went on to develop exudation in subsequent visits. Overall, 8 of the 10 eyes with nonexudative CNV developed exudation with a mean time of 8 months and mean CNV area growth rate of 20% per month (P = 0.014, exponential model). Initiation of antiangiogenic treatment halted their growth. In comparison, exudation occurred in only 6 of the 53 eyes (11%) that lacked a precursor nonexudative CNV. Cox proportional hazard analysis showed that having nonexudative CNV detected was associated with an 18.1-fold increase in the rate of exudation subsequently developing (P < 0.0001).

Conclusions: Nonexudative CNV frequently is detected by OCTA in the fellow eyes of those with exudative CNV. These lesions carry a high risk of exudation developing within the first year after detection and could benefit from close monitoring. The high risk of progression may justify prophylactic treatment; further studies are needed.
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http://dx.doi.org/10.1016/j.oret.2019.03.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6684834PMC
August 2019

Maximum value projection produces better OCT angiograms than mean value projection.

Biomed Opt Express 2018 Dec 26;9(12):6412-6424. Epub 2018 Nov 26.

Casey Eye Institute, Oregon Health & Science University, Portland, OR 27239, USA.

Optical coherence tomography angiography (OCTA) images rely on data projections for both qualitative and quantitative interpretation. Both maximum value and mean value projections are commonly used, and many researchers consider them essentially interchangeable approaches. On the contrary, we find that maximum value projection achieves a consistently higher signal-to-noise ratio and higher image contrast across multiple vascular layers, in both healthy eyes and for each disease examined.
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http://dx.doi.org/10.1364/BOE.9.006412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6491019PMC
December 2018

DETECTION OF CLINICALLY UNSUSPECTED RETINAL NEOVASCULARIZATION WITH WIDE-FIELD OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

Retina 2020 May;40(5):891-897

Department of Ophthalmology, Casey Eye Institute, Oregon Health and Science University, Portland, Oregon; and.

Purpose: To evaluate wide-field optical coherence tomography angiography (OCTA) for detection of clinically unsuspected neovascularization (NV) in diabetic retinopathy (DR).

Methods: This prospective observational single-center study included adult patients with a clinical diagnosis of nonproliferative DR. Participants underwent a clinical examination, standard 7-field color photography, and OCTA with commercial and prototype swept-source devices. The wide-field OCTA was achieved by montaging five 6 × 10-mm scans from a prototype device into a 25 × 10-mm image and three 6 × 6-mm scans from a commercial device into a 15 × 6-mm image. A masked grader determined the retinopathy severity from color photographs. Two trained readers examined conventional and wide-field OCTA images for the presence of NV.

Results: Of 27 participants, photographic grading found 13 mild, 7 moderate, and 7 severe nonproliferative DR. Conventional 6 × 6-mm OCTA detected NV in 2 eyes (7%) and none with 3 × 3-mm scans. Both prototype and commercial wide-field OCTA detected NV in two additional eyes. The mean area of NV was 0.38 mm (range 0.17-0.54 mm). All eyes with OCTA-detected NV were photographically graded as severe nonproliferative DR.

Conclusion: Wide-field OCTA can detect small NV not seen on clinical examination or color photographs and may improve the clinical evaluation of DR.
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http://dx.doi.org/10.1097/IAE.0000000000002487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6722037PMC
May 2020

Invariant features-based automated registration and montage for wide-field OCT angiography.

Biomed Opt Express 2019 Jan 11;10(1):120-136. Epub 2018 Dec 11.

Casey Eye Institute, Oregon Health & Science University, Portland, OR 97239, USA.

The field of view of optical coherence tomography angiography (OCTA) images of the retina can be increased by montaging consecutive scans acquired at different retinal regions. Given the dramatic variation in aberrations throughout the entire posterior pole region, it is challenging to achieve seamless merging with apparent capillary continuity across the boundaries between adjacent angiograms. For this purpose, we propose herein a method that performs automated registration of contiguous OCTA images based on invariant features and uses a novel montage algorithm. The invariant features were used to register the overlapping areas between adjacently located scans by estimating the affine transformation matrix needed to accurately stitch them. Then, the flow signal was compensated to homogenize the angiograms with different brightness and the joints were blended to generate a seamless, montaged wide-field angiogram. We evaluated the algorithm on normal and diabetic retinopathy eyes. The proposed method could montage the angiograms seamlessly and provided a wide-field of view of retinal vasculature.
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http://dx.doi.org/10.1364/BOE.10.000120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6363196PMC
January 2019

Medicare Incentive Payments to United States Ophthalmologists for Use of Electronic Health Records: 2011-2016.

Ophthalmology 2019 07 13;126(7):928-934. Epub 2019 Feb 13.

Department of Ophthalmology, University of Washington, Seattle, Washington.

Purpose: To investigate ophthalmologists' rate of attestation to meaningful use (MU) of their electronic health record (EHR) systems in the Medicare EHR Incentive Program and their continuity and success in receiving payments in comparison with other specialties.

Design: Administrative database study.

Participants: Eligible professionals participating in the Medicare EHR Incentive Program.

Methods: Based on publicly available data sources, subsets of payment and attestation data were created for ophthalmologists and for other specialties. The number of eligible professionals attesting was determined using the attestation data for each year and stage of the program. The proportion of attestations by EHR vendor was calculated using all attestations for each vendor.

Main Outcome Measures: Numbers of ophthalmologists attesting by year and stage of the Medicare EHR Incentive Program, incentive payments, and number of attestations by EHR vendor.

Results: In the peak year of participation, 51.6% of ophthalmologists successfully attested to MU, compared with 37.1% of optometrists, 50.2% of dermatologists, 54.5% of otolaryngologists, and 64.4% of urologists. Across the 6 years of the program, ophthalmologists received an average of $17 942 in incentive payments compared with $11 105 for optometrists, $16 617 for dermatologists, $20 203 for otolaryngologists, and $23 821 for urologists. Epic and Nextgen were the most frequently used EHRs for attestation by ophthalmologists.

Conclusions: Ophthalmology as a specialty performed better than optometry and dermatology, but worse than otolaryngology and urology, in terms of the proportion of eligible professionals attesting to MU of EHRs. Ophthalmologists were more likely to remain in the program after their initial year of attestation compared with all eligible providers. The top 4 EHR vendors accounted for 50% of attestations by ophthalmologists.
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http://dx.doi.org/10.1016/j.ophtha.2019.01.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6662572PMC
July 2019

Culture-Proven Endophthalmitis After Intravitreal Injection: A 10-Year Analysis.

Ophthalmic Surg Lasers Imaging Retina 2019 01;50(1):33-38

Background And Objective: To report on the microbiology, management, and visual outcomes of intravitreal injection (IVI)-associated, culture-proven endophthalmitis.

Patients And Methods: All patients seen at a tertiary referral center with culture-proven endophthalmitis associated with an IVI between June 2007 and July 2017 were included in this retrospective analysis.

Results: Thirty-five patients with culture-positive endophthalmitis following IVI were identified. All gram-positive organisms (34 of 35) were susceptible to vancomycin. Cases due to pathogens associated with oral or respiratory flora were common (31.4%, n = 11), presented earlier (2.0 days vs. 4.6 days, P < .001), were more likely to undergo pars plana vitrectomy (81.8% vs. 25.0%, P = .002) and had worse visual acuity outcomes.

Conclusion: IVI-associated endophthalmitis pathogens and anti-microbial susceptibilities in the Pacific Northwest are similar to those reported from other geographic locations. Bacteria associated with the oral and respiratory flora are common isolates that result in a more aggressive course and worse visual outcomes. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:33-38.].
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http://dx.doi.org/10.3928/23258160-20181212-05DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875494PMC
January 2019

MEDnet, a neural network for automated detection of avascular area in OCT angiography.

Biomed Opt Express 2018 Nov 2;9(11):5147-5158. Epub 2018 Oct 2.

Casey Eye Institute, Oregon Health & Science University, Portland, OR 97239, USA.

Screening and assessing diabetic retinopathy (DR) are essential for reducing morbidity associated with diabetes. Macular ischemia is known to correlate with the severity of retinopathy. Recent studies have shown that optical coherence tomography angiography (OCTA), with intrinsic contrast from blood flow motion, is well suited for quantified analysis of the avascular area, which is potentially a useful biomarker in DR. In this study, we propose the first deep learning solution to segment the avascular area in OCTA of DR. The network design consists of a multi-scaled encoder-decoder neural network (MEDnet) to detect the non-perfusion area in 6 × 6 mm and in ultra-wide field retinal angiograms. Avascular areas were effectively detected in DR subjects of various disease stages as well as in the foveal avascular zone of healthy subjects.
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http://dx.doi.org/10.1364/BOE.9.005147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6238913PMC
November 2018

Quantitative Evaluation of Choroidal Neovascularization under Pro Re Nata Anti-Vascular Endothelial Growth Factor Therapy with OCT Angiography.

Ophthalmol Retina 2018 Sep 2;2(9):931-941. Epub 2018 Mar 2.

Casey Eye Institute, Oregon Health & Science University, Portland, OR 97239, USA.

Purpose: To use optical coherence tomography angiography (OCTA) derived quantitative metrics to assess the response of choroidal neovascularization to pro-re-nata (PRN) anti-endothelial growth factor (anti-VEGF) treatment in neovascular age-related macular degeneration (AMD).

Design: Prospective longitudinal cohort study.

Participants: Fourteen eyes from 14 study participants with treatment-naïve neovascular AMD were enrolled.

Methods: Subjects were evaluated monthly and treated with intravitreal anti-VEGF agents under a PRN protocol for one year. At each visit, two 3×3 mm OCTA scans were obtained. Custom image processing was applied to segment the outer retinal slab, suppress projection artifact, and automatically detect CNV. CNV membrane area (mm) and CNV vessel area (mm) was calculated.

Main Outcomes: Individual and mean CNV membrane area and CNV vessel area at each visit; within-visit repeatability determined by coefficient of variation.

Results: Eight eyes had entire CNV within 3×3 mm scanning area and had adequate image quality for CNV quantification. One case (case #2) was excluded from analysis due to the presence of a large subretinal hemorrhage overlying the CNV membrane. In the remaining cases, CNV vessel area was reduced by 39%, 50%, 43%, and 41% at months 1, 3, 6, and 12 respectively. CNV membrane area was reduced by 39%, 51%, 54%, and 45% at months 1, 3, 6, and 12. At month 6, mean change from baseline was not statistically significant for CNV vessel area, while it was statistically significant for CNV membrane area. Neither metric was significantly different compared to baseline at month 12. Individual analyses revealed each CNV had a unique response under PRN treatment. Within-visit repeatability was was 7.96% (coefficient of variation) for CNV vessel area and 7.37% for CNV membrane area.

Conclusions: In this small exploratory study of CNV response to PRN anti-VEGF treatment, both CNV vessel area and membrane area were reduced compared to baseline after three months. After one year of follow-up, these reductions were no longer statistically significant. When anti-VEGF treatment was held, increasing CNV vessel area over time often resulted in exudation, but it was not possible to exactly when exudation occurs.
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http://dx.doi.org/10.1016/j.oret.2018.01.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6139650PMC
September 2018

Plexus-Specific Detection of Retinal Vascular Pathologic Conditions with Projection-Resolved OCT Angiography.

Ophthalmol Retina 2018 Aug 10;2(8):816-826. Epub 2018 Jan 10.

Casey Eye Institute, Oregon Health & Science University, 3375 SW Terwilliger Blvd, Portland, OR 97239.

Objective: To evaluate the projection-resolved (PR) optical coherence tomography angiography (OCTA) algorithm in detecting plexus-specific vascular abnormalities in retinal pathologies.

Design: Cross-sectional observational clinical study.

Participants: Patients diagnosed with retinal vascular diseases and healthy volunteers.

Methods: Eyes were imaged using an OCT system operating at 840 nm and employing the split-spectrum amplitude decorrelation algorithm. A novel algorithm suppressed projection artifacts inherent to OCTA. The volumetric scans were segmented and visualized on different plexuses.

Main Outcome Measures: Qualitative observation of vascular abnormalities on both cross-sectional and PR-OCTA images.

Results: Eight illustrative cases are reported. In cases of diabetic retinopathy, retinal vessel occlusion, and retinitis pigmentosa, PR-OCTA detected retinal nonperfusion regions within deeper retinal plexuses not visualized by conventional OCTA. In age-related macular degeneration, cross-sectional PR-OCTA permitted the classification of choroidal neovascularization, and, in a case of retinal angiomatous proliferation, identified a vertical vessel contiguous with the deep capillary plexus. In macular telangiectasia, PR-OCTA detected a diving perifoveal vein and delineated subretinal neovascularization.

Conclusions: Application of PR-OCTA promises to improve sensitive, accurate evaluation of individual vascular plexuses in multiple retinal diseases.
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http://dx.doi.org/10.1016/j.oret.2017.11.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6106769PMC
August 2018

Automated Quantification of Nonperfusion Areas in 3 Vascular Plexuses With Optical Coherence Tomography Angiography in Eyes of Patients With Diabetes.

JAMA Ophthalmol 2018 08;136(8):929-936

Casey Eye Institute, Oregon Health and Science University, Portland.

Importance: Diabetic retinopathy (DR) is a leading cause of vision loss that is managed primarily through qualitative clinical examination of the retina. Optical coherence tomography angiography (OCTA) may offer an objective and quantitative method of evaluating DR.

Objective: To quantify capillary nonperfusion in 3 vascular plexuses in the macula of eyes patients with diabetes of various retinopathy severity using projection-resolved OCTA (PR-OCTA).

Design, Setting, And Participants: Cross-sectional study at a tertiary academic center comprising 1 eye each from healthy control individuals and patients with diabetes at different severity stages of retinopathy. Data were acquired and analyzed between January 2015 and December 2017.

Main Outcomes And Measures: Foveal avascular zone area, extrafoveal avascular area (EAA), and the sensitivity of detecting levels of retinopathy.

Results: The study included 39 control individuals (20 women [51%]; mean [SD] age, 43.41 [19.37] years); 16 patients with diabetes without retinopathy (8 women [50%]; mean [SD] age, 56.50 [12.43] years); 23 patients with mild to moderate nonproliferative DR (18 women [78%] ; mean [SD] age, 62.48 [10.55] years); and 32 patients with severe nonproliferative DR or proliferative DR (12 women [38%]; mean age, 53.41 [14.05] years). Mean (SD) foveal avascular zone area was 0.203 (0.103) mm2 for control individuals, 0.192 (0.084) mm2 for patients with diabetes without retinopathy, 0.243 [0.079] mm2 for mild to moderate nonproliferative DR, and 0.359 (0.275) mm2 for severe nonproliferative DR or proliferative DR. Mean (SD) EAA in whole inner retinal slab in these groups, respectively, were 0.020 (0.031) mm2, 0.034 (0.047) mm2, 0.038 (0.040) mm2, and 0.237 (0.235) mm2. The mean (SD) sum of EAA from 3 segmented plexuses in each of the respective groups were 0.103 (0.169) mm2, 0.213 (0.242) mm2, 0.451 (0.243) mm2, and 1.325 (1.140) mm2. With specificity fixed at 95%, using EAA in inner retinal slab, the sensitivity of detecting patients with diabetes from healthy control individuals was 28% (95% CI, 18%-40%), 31% for patients with DR (95% CI, 19%-45%), and 47% for patients with severe DR (95% CI, 29%-65%) from whole inner retinal EAA. With the sum of EAA from 3 individual plexuses, the sensitivities were 69% (95% CI, 57%-80%), 82% (95% CI, 70%-91%), and 97% (95% CI, 85%-100%), respectively. Avascular areas were not associated with signal strength index. The commercial vessel density from the 2-plexus scheme distinguished the groups with lower sensitivity and were dependent on SSI.

Conclusions And Relevance: Automatically quantified avascular areas from a 3-layer segmentation scheme using PR-OCTA distinguished levels of retinopathy with a greater sensitivity than avascular areas from unsegmented inner retinal slab or measurements from a commercially available vessel density in 2-layer scheme. Additional studies are needed to investigate the applicability of nonperfusion parameters in clinical settings.
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http://dx.doi.org/10.1001/jamaophthalmol.2018.2257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6142939PMC
August 2018

Automated detection of photoreceptor disruption in mild diabetic retinopathy on volumetric optical coherence tomography.

Biomed Opt Express 2017 Dec 7;8(12):5384-5398. Epub 2017 Nov 7.

Casey Eye Institute, Oregon Health & Science University, Portland, OR, 97239, USA.

Diabetic retinopathy is a pathology where microvascular circulation abnormalities ultimately result in photoreceptor disruption and, consequently, permanent loss of vision. Here, we developed a method that automatically detects photoreceptor disruption in mild diabetic retinopathy by mapping ellipsoid zone reflectance abnormalities from optical coherence tomography images. The algorithm uses a fuzzy c-means scheme with a redefined membership function to assign a defect severity level on each pixel and generate a probability map of defect category affiliation. A novel scheme of unsupervised clustering optimization allows accurate detection of the affected area. The achieved accuracy, sensitivity and specificity were about 90% on a population of thirteen diseased subjects. This method shows potential for accurate and fast detection of early biomarkers in diabetic retinopathy evolution.
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http://dx.doi.org/10.1364/BOE.8.005384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5745090PMC
December 2017

Automated drusen detection in dry age-related macular degeneration by multiple-depth, optical coherence tomography.

Biomed Opt Express 2017 Nov 17;8(11):5049-5064. Epub 2017 Oct 17.

Casey Eye Institute, Oregon Health & Science University, Portland, OR, 27239, USA.

We introduce a method to automatically detect drusen in dry age-related macular degeneration (AMD) from optical coherence tomography with minimum need for layer segmentation. The method is based on the detection of drusen areas in C-scans at certain distances above the Bruch's membrane, circumventing the difficult task of pathologic retinal pigment epithelium segmentation. All types of drusen can be detected, including the challenging subretinal drusenoid deposits (pseudodrusen). The high sensitivity and accuracy demonstrated here shows its potential for detection of drusen onset in early AMD.
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http://dx.doi.org/10.1364/BOE.8.005049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5695952PMC
November 2017