Justis P. Ehlers

Machine Learning-Based Automated Detection and Quantification of Geographic Atrophy and Hypertransmission Defects Using Spectral Domain Optical Coherence Tomography

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The current study describes the development and assessment of innovative, machine learning (ML)-based approaches for automated detection and pixel-accurate measurements of regions with geographic atrophy (GA) in late-stage age-related macular degeneration (AMD) using optical coherence tomography systems. 900 OCT volumes, 100266 B-scans, and en face OCT images from 341 non-exudative AMD patients with or without GA were included in this study from both Cirrus (Zeiss) and Spectralis (Heidelberg) OCT systems. B-scan and en face level ground truth GA masks were created on OCT B-scan where the segmented ellipsoid zone (EZ) line, retinal pigment epithelium (RPE) line, and bruchs membrane (BM) line overlapped. Two deep learning-based approaches, B-scan level and en face level, were trained. The OCT B-scan model had detection accuracy of 91% and GA area measurement accuracy of 94%. The en face OCT model had detection accuracy of 82% and GA area measurement accuracy of 96% with primary target...

OCT-Derived Radiomic Features Predict Anti–VEGF Response and Durability in Neovascular Age-Related Macular Degeneration

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No established biomarkers currently exist for therapeutic efficacy and durability of anti–VEGF therapy in neovascular age-related macular degeneration (nAMD). This study evaluated radiomic-based quantitative OCT biomarkers that may be predictive of anti-VEGF treatment response and durability. Design Assessment of baseline biomarkers using machine learning (ML) classifiers to predict tolerance to anti-VEGF therapy. Participants Eighty-one participants with treatment-naïve nAMD from the OSPREY study, including 15 super responders (patients who achieved and maintained retinal fluid resolution) and 66 non–super responders (patients who did not achieve or maintain retinal fluid resolution). Methods A total of 962 texture-based radiomic features were extracted from fluid, subretinal hyperreflective material (SHRM), and different retinal tissue compartments of OCT scans. The top 8 features, chosen by the minimum redundancy maximum relevance feature selection method, were e...

Automated Machine Learning Detection of Hydroxychloroquine Toxicity and Prediction of Future Toxicity Using Higher Order OCT Biomarkers

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Objective: Despite guidelines for HCQ toxicity screening, there are clear challenges to accurate detecting and interpretation. In the current report, the feasibility of automated machine-learning (ML) -based detection of hydroxychloroquine (HCQ) retinopathy and prediction of progression to toxicity in eyes without preexisting toxicity is described. Design: Retrospective longitudinal cohort study. Subjects and methods: This was an IRB-approved retrospective longitudinal image analysis study of 388 subjects on hydroxychloroquine. Multi-layer compartmental retinal segmentation with EZ mapping was utilized to harvest quantitative SDOCT biomarkers. Utilizing a combination of clinical features (i.e., cumulative HCQ dose, duration of therapy) and quantitative imaging biomarkers (e.g., volumetric ellipsoid zone (EZ) integrity and compartmental measurements), machine learning models were created to detect toxicity and predict progression based on ground truth OCT-based toxicity reads by 2 ma...

Impact of Baseline Quantitative OCT Features on Response to Risuteganib for the Treatment of Dry AMD-The Importance of Outer Retinal Integrity

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Objective: The purpose of the study was to perform a post-hoc analysis to explore the effect of baseline anatomic characteristics identified on optical coherence tomography (OCT) on best-corrected visual acuity (BCVA) response with risuteganib from the completed Phase 2 study in subjects with dry age-related macular degeneration. Design: Post-hoc analysis of a randomized, double-masked, placebo-controlled Phase 2 study SUBJECTS, PARTICIPANTS, AND/OR CONTROLS: Eyes with intermediate dry AMD with BCVA between 20/40-20/200. Patients with concurrent vision impacting or macula obscuring ocular pathology were excluded. Methods: Patients were randomized to receive intravitreal 1.0 mg ristuteganib or sham injection at baseline. A second 1.0mg intravitreal injection of risuteganib was given at week 16 in the treatment arm. Two independent masked reading centers evaluated baseline anatomic characteristics on OCT to explore for features associated with positive response to risuteganib. Main ou...

Risk Classification for Progression to Subfoveal Geographic Atrophy in Dry Age-Related Macular Degeneration Using Machine Learning–Enabled Outer Retinal Feature Extraction

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Background and objective: To evaluate the utility of spectral-domain optical coherence tomography biomarkers to predict the development of subfoveal geographic atrophy (sfGA). Patients and methods: This was a retrospective cohort analysis including 137 individuals with dry age-related macular degeneration without sfGA with 5 years of follow-up. Multiple spectral-domain optical coherence tomography quantitative metrics were generated, including ellipsoid zone (EZ) integrity and subretinal pigment epithelium (sub-RPE) compartment features. Results: Reduced mean EZ-RPE central subfield thickness and increased sub-RPE compartment thickness were significantly different between sfGA convertors and nonconvertors at baseline in both 2-year and 5-year sfGA risk assessment. Longitudinal change assessment showed a significantly higher degradation of EZ integrity in sfGA convertors. The predictive performance of a machine learning classification model based on 5-year and 2-year risk conversion ...

The Emerging Role of Intraoperative OCT for Retinal Surgery: Image-guided technologies are rapidly advancing

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O ptical coherence tomography (OCT) is a quick and noninvasive imaging modality capable of discerning high-resolution morphologic features of the retina and surrounding structures. 1 Over the past 20 years, OCT has evolved to become an integral component of ophthalmic diagnosis, management, and therapeutic monitoring, with an estimated tens of millions of images captured per year. 2 During this time, improvements in OCT technology have enabled the transition from an outpatient imaging modality to the operating room. Integration of OCT into the operating room was initially limited by the bulky equipment and design of clinical systems that required patients to be cooperative and positioned upright. This hurdle was overcome through the development of the handheld OCT, introduced to the surgical suite in 2009, which allowed imaging of patients who were supine and under anesthesia. 3 This system was further updated to a microscope-mounted OCT configuration, which served to ameliorate pre...

Vitreomacular Traction Surgery from the DISCOVER Study: Intraoperative OCT Utility, Ellipsoid Zone Dynamics, and Outcomes

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BACKGROUND AND OBJECTIVES: To characterize the clinical and ellipsoid zone (EZ) integrity outcomes in surgical intervention for symptomatic vitreomacular traction (VMT), and to evaluate the utility of intraoperative optical coherence tomography (OCT) during VMT surgery. PATIENTS AND METHODS: This was a post-hoc analysis of eyes in the DISCOVER study undergoing pars plana vitrectomy (PPV) with intraoperative OCT for VMT-related macular disease. Data were collected prospectively on feasibility and utility of intraoperative OCT, with follow-up lasting 12 months. RESULTS: Forty-three eyes of 41 patients were included and mean visual acuity improved from 20/96 to 20/45 ( P < .001). Intraoperative OCT provided information that impacted surgical decision-making in eight patients (18.6%). EZ integrity metrics significantly improved from baseline to 12 months and directly correlated with functional outcomes ( P < .001). CONCLUSIONS: Retinal function and morphology improved significantl...

Multi-Compartment Spatially-derived Radiomics from Optical Coherence Tomography Predict Anti-VEGF Treatment Durability in Macular Edema Secondary to Retinal Vascular Disease

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Objective: Diabetic macular edema (DME) and retinal vein occlusion (RVO) are the leading causes of visual impairments across the world. Vascular endothelial growth factor (VEGF) stimulates breakdown of blood-retinal barrier that causes accumulation of fluid within macula. Anti-VEGF therapy is the first-line treatment for both the diseases; however, the degree of response varies for individual patients. The main objective of this work was to identify the (i) texture-based radiomics features within individual fluid and retinal tissue compartments of baseline spectral-domain optical coherence tomography (SD-OCT) images and (ii) the specific spatial compartments that contribute most pertinent features for predicting therapeutic response. Methods: A total of 962 texture-based radiomics features were extracted from each of the fluid and retinal tissue compartments of OCT images, obtained from the PERMEATE study. Top-performing features selected from the consensus of different feature sele...

Longitudinal Higher-Order OCT Assessment of Quantitative Fluid Dynamics and the Total Retinal Fluid Index in Neovascular AMD

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Purpose : The purpose of this study was to evaluate the feasibility of assessing quantitative longitudinal fluid dynamics and total retinal fluid indices (TRFIs) with higher-order optical coherence tomography (OCT) for neovascular age-related macular degeneration (nAMD). Methods : A post hoc image analysis study was performed using the phase II OSPREY clinical trial comparing brolucizumab and aflibercept in nAMD. Higher-order OCT analysis using a machine learning−enabled fluid feature extraction platform was used to segment intraretinal fluid (IRF) and subretinal fluid (SRF) volumetric components. TRFI, the proportion of fluid volume against total retinal volume, was calculated. Longitudinal fluid metrics were evaluated for the following groups: all subjects (i.e. treatment agnostic), brolucizumab, and aflibercept. Results : Mean IRF and SRF volumes were significantly reduced from baseline at each timepoint for all groups. Fluid feature extraction allowed high-resolution asses...

Epiretinal Membrane Surgery Using Intraoperative OCT-guided Membrane Removal in the DISCOVER Study versus Conventional Membrane Removal

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Purpose: To provide a comparative assessment of clinical outcomes between subjects undergoing intraoperative optical coherence tomography (OCT) and conventional surgery for pars plana vitrectomy (PPV) with epiretinal membrane (ERM) peel. Design: Case-control retrospective comparative assessment SUBJECTS: Subjects undergoing PPV with membrane peel for ERMs with eyes pooled from the prospective intraoperative OCT (iOCT) DISCOVER study and eyes undergoing conventional ERM surgery without intraoperative OCT. Methods: Visual acuity and OCT assessment before ERM surgery and at 1-, 3-, 6-, and 12-month follow up after standard small gauge pars plana vitrectomy (PPV) with iOCT feedback (iOCT DISCOVER group) or PPV with compulsory ILM peeling (conventional group). Visual acuity, central subfield thickness (CST), re-operation rate and ERM recurrence were determined by record review and post-hoc assessment of clinical OCTs after ERM peel. Main outcome measures: Visual acuity and ERM recurrence...

Aqueous Cytokine Expression and Higher-Order OCT Biomarkers: Assessment of the Anatomic-Biologic Bridge in the Imagine Dme Study

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Purpose To identify biomarkers for predicting response to anti-VEGF therapy in diabetic macular edema (DME) and evaluate any links between cytokine expression and OCT phenotype. Design IMAGINE DME is a post-hoc image analysis and cytokine expression assessment of the DAVE randomized clinical trial. Methods Subjects were categorized as anatomical Responders or Nonresponders,and within the Responder group as Rebounders and Nonrebounders based on quantitative, longitudinal optical coherence tomography (OCT) criteria. Retinal layer and fluid features were extracted using an OCT machine-learning augmented segmentation platform. Responders were further sub-classified by rapidity of response. Aqueous concentrations of 54 cytokines at multiple timepoints. Expression was compared between Responder groups and correlated with OCT imaging biomarkers. Results Of the 24 eyes studied, 79% were anatomical Responders with 38% Super Responders, 17% Early Responders, 25% Slow Responders. Twenty-one pe...

Concerns about the interpretation of OCT and fundus findings in COVID-19 patients in recent Lancet publication

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We read with great interest the correspondence in Lancet by Marinho et al. [ 1 ] describing purported retinal manifestations of coronavirus disease (COVID-19). While there is great interest to understand potential ocular complications of COVID-19 during this pandemic, we have some concerns regarding the interpretation of the fundus and optical coherence tomography (OCT) findings. Marinho et al. examined 12 COVID-19 patients (all confirmed by PCR or antibody testing) with typical systemic disease but no visual symptoms. The reported cohort was relatively young (25–69 years; no mean or median provided) without severe systemic disease, although 2 were hospitalized. Eleven of the 12 were physicians or health care workers. The authors reported that 4 of the 12 patients displayed lesions consistent with subtle cotton wool spots (CWSs), i.e., retinal nerve fiber layer (NFL) infarcts, and illustrated one example lesion. It should be noted that CWSs can be identified in a broad spectru...

iOCT-assisted macular hole surgery: outcomes and utility from the DISCOVER study

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Background/aims This study aimed to characterise the clinical outcomes and utility of intraoperative optical coherence tomography (iOCT)-assisted macular hole (MH) repair. Methods This was a post hoc analysis of eyes in the D etermination of feasibility of I ntraoperative S pectral domain microscope C ombined/integrated O CT V isualization during E n face R etinal and ophthalmic surgery (DISCOVER) study undergoing surgical MH repair with use of iOCT. Functional and surgical outcome data were collected through 12 months postoperatively. MH closure rate, postoperative visual acuity (VA), percentage of cases in which iOCT provided valuable feedback and altered surgical decision making were measured. Results Eighty-four eyes were included in this study. The mean preoperative VA measured 20/114. The mean postoperative VA improved to 20/68 (p<0.001) at month 1, 20/48 (p<0.001) at month 3 and 20/45 (p<0.001) at month 12 or later. In 43 cases (51%), surgeons reported that iOCT prov...

Intraoperative OCT-Assisted Retinal Detachment Repair in the DISCOVER Study: Impact and Outcomes

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Purpose The purpose of this study is to evaluate intraoperative OCT (iOCT) utility and outcomes during retinal detachment (RD) repair. Design The DISCOVER intraoperative OCT study is a prospective IRB-approved study. Subjects Subjects in the DISCOVER study undergoing surgical repair for RD. Methods This was a post-hoc analysis of eyes in the DISCOVER study undergoing surgical repair for retinal detachments. Inclusion criteria included iOCT following perfluorocarbon liquid (PFO) placement and at least 6 months follow-up. Exclusion criteria included severe retinal pathology unrelated to RD. Surgeons completed standardized questionnaires after each case evaluating the iOCT instrument’s utility. Functional and surgical outcome data was collected at the latest available time point between 6 or 12 months. Outcomes were evaluated in 2 groups: uncomplicated primary and complex cases. Main Outcome Measures Intraoperative OCT utility, single-surgery success, visual acuity outcomes Resul...

Advances In Intraoperative OCT

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Over the past decade, there have been major advances in the field of intraoperative optical coherence tomography. From the development of the portable OCT probe to the first microscope-integrated system, intraoperative OCT has evolved from a research idea to a clinically viable technology. Advances such as heads-up visualization and microscope-integration, as well as the results from large clinical studies, have pushed the field forward. While the feasibility and potential utility of intraoperative optical coherence tomography has been demonstrated both in clinical studies and in real-world usage, several areas of enhancement are needed to enable iOCT to be part of a seamless surgical feedback platform. Image quality, improved efficiency, OCT-compatible surgical instrumentation, automated analysis software, instrument tracking systems and enhanced visualization systems are all areas of focus for improvement for the future. This update will focus on iOCT’s development, especial...

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