Sunil K. Srivastava

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...

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...

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...

Intraoperative Optical Coherence Tomography-Assisted Descemet Membrane Endothelial Keratoplasty in the DISCOVER Study: First 100 Cases

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Purpose Intraoperative optical coherence tomography (iOCT) may facilitate successful transition to descemet membrane endothelial keratoplasty (DMEK) surgery via improved efficiency of tissue orientation. The purpose of this study is to report a large consecutive series of iOCT-assisted DMEK, inclusive of all learning curve cases. Design Prospective consecutive case series. Methods The Determination of Feasibility of Intraoperative Spectral Domain Microscope Combined/Integrated OCT Visualization During En Face Retinal and Ophthalmic Surgery (DISCOVER) study is a single-site, multi-surgeon, IRB-approved investigational device prospective study. The first 100 consecutive iOCT-assisted DMEK surgeries performed by one attending corneal surgeon (JMG) and six novice surgeons (cornea fellows under supervision) were reviewed. iOCT was utilized for tissue orientation. Patient demographics, tissue characteristics, intraoperative parameters and postoperative complications are reported. Outcomes...

Ultra-widefield Fluorescein Angiography and Optical Coherence Tomography Findings in Tubulointerstitial Nephritis and Uveitis Syndrome

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Purpose To report the spectrum of posterior segment findings in tubulointerstitial nephritis and uveitis syndrome (TINU) and discuss the abnormalities that can be seen on imaging. Design Retrospective, consecutive case series. Participants Patients with TINU and posterior segment manifestations on exam or imaging. Methods Patients with elevated urine beta-2 microglobulin (Uβ2M) and a diagnosis of TINU were included if they were evaluated at the Cole Eye Institute and did not have alternative etiologies for uveitis. Electronic medical records were reviewed for abnormal findings on ultra-widefield fluorescein angiography (UWFFA) and optical coherence tomography (OCT). Main Outcome Measures Presence of peripheral vascular leakage, optic disc leakage, chorioretinal lesions or leakage within the macula on UWFFA. For OCT findings, patients were categorized as having intraretinal fluid, epiretinal membrane, or optic nerve edema. Results Twenty eyes from 10 patients (6 female, 4 male) ...

Optical coherence tomography angiography characteristics of choroidal neovascularization requiring varied dosing frequencies in treat-and-extend management: An analysis of the AVATAR study

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Purpose To evaluate optical coherence tomography angiography (OCTA) characteristics of choroidal neovascularization (CNV) in eyes requiring different treatment frequency of anti-vascular endothelial growth factor (VEGF) therapy for neovascular age-related macular degeneration (NVAMD). Design Prospective observational case series. Methods Subjects who had undergone anti-VEGF treatment for NVAMD in the AVATAR study were subdivided into 3 groups depending on required anti-VEGF dosing: (i) treat-and-extend requiring every 4–6 weeks dosing (TEq4-6w), (ii) treat-and-extend requiring every 7–12 weeks dosing (TEq7-12w), (iii) eyes not requiring injection within last 12 months (PRN >12mo). OCTA images were evaluated for the morphological characteristics of CNV and the choriocapillaris flow void. Results Study consisted 40 eyes of 31 patients with a mean age of 79.9 ± 6.2 years. CNV morphology analysis on OCTA was feasible in 29 (73%) eyes. Ninety percent of CNVs in TEq7...


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Purpose: To compare optical coherence tomography angiography ( OCTA ) review strategies for optimizing choroidal neovascularization ( CNV ) detection . Methods: Eyes with CNV in the differential diagnosis were imaged with the Avanti RTVue XR HD (Optovue, Fremont, CA). Three modalities of review for CNV presence were used in each case: a single report generated using automated segmentation within Avanti software; a continuous slab descent video OCTA export; and a manual segmentation approach using cross-sectional OCT with decorrelation signal overlay. Scans were reviewed by two masked expert reviewers; a third reviewer was used for discrepancies. Results: The study included 421 eyes, and 350 eyes had reports deemed sufficient quality for interpretation. Choroidal neovascularization was in the differential diagnosis in 107 of 350 patients. Overall CNV was identified in 55% (59/107) eyes. In those eyes with CNV , the automated segmentation identified CNV in 56% (33/59) of cases, contin...


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