Dataset Information

Texture-Based Radiomic SD-OCT Features Associated With Response to Anti-VEGF Therapy in a Phase III Neovascular AMD Clinical Trial.

ABSTRACT:

Purpose

The goal of this study was to evaluate the role of texture-based baseline radiomic features (Fr) and dynamic radiomics alterations (delta, FΔr) within multiple targeted compartments on optical coherence tomography (OCT) scans to predict response to anti-vascular endothelial growth factor (VEGF) therapy in neovascular age-related macular degeneration (nAMD).

Methods

HAWK is a phase 3 clinical trial data set of active nAMD patients (N = 1082) comparing brolucizumab and aflibercept. This analysis included patients receiving 6 mg brolucizumab or 2 mg aflibercept and categorized as complete responders (n = 280) and incomplete responders (n = 239) based on whether or not the eyes achieved/maintained fluid resolution on OCT. A total of 481 Fr were extracted from each of the fluid, subretinal hyperreflective material (SHRM), retinal tissue, and sub-retinal pigment epithelium (RPE) compartments. Most discriminating eight baseline features, selected by the minimum redundancy, maximum relevance feature selection, were evaluated using a quadratic discriminant analysis (QDA) classifier on the training set (Str, n = 363) to differentiate between the two patient groups. Classifier performance was subsequently validated on independent test set (St, n = 156).

Results

In total, 519 participants were included in this analysis from the HAWK phase 3 study. There were 280 complete responders and 219 incomplete responders. Compartmental analysis of radiomics featured identified the sub-RPE and SHRM compartments as the most distinguishing between the two response groups. The QDA classifier yielded areas under the curve of 0.78, 0.79, and 0.84, respectively, using Fr, FΔr, and combined Fr, FΔr, and Fc on St.

Conclusions

Utilizing compartmental static and dynamic radiomics features, unique differences were identified between eyes that respond differently to anti-VEGF therapy in a large phase 3 trial that may provide important predictive value.

Translational relevance

Imaging biomarkers, such as radiomics features identified in this analysis, for predicting treatment response are needed to enhanced precision medicine in the management of nAMD.

SUBMITTER: Sil Kar S

PROVIDER: S-EPMC10833054 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Publications

Texture-Based Radiomic SD-OCT Features Associated With Response to Anti-VEGF Therapy in a Phase III Neovascular AMD Clinical Trial.

Sil Kar Sudeshna S Cetin Hasan H Srivastava Sunil K SK Madabhushi Anant A Ehlers Justis P JP

Translational vision science & technology 20240101 1

<h4>Purpose</h4>The goal of this study was to evaluate the role of texture-based baseline radiomic features (Fr) and dynamic radiomics alterations (delta, FΔr) within multiple targeted compartments on optical coherence tomography (OCT) scans to predict response to anti-vascular endothelial growth factor (VEGF) therapy in neovascular age-related macular degeneration (nAMD).<h4>Methods</h4>HAWK is a phase 3 clinical trial data set of active nAMD patients (N = 1082) comparing brolucizumab and aflib ...[more]

PMID: 38289610

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Project description:PurposeNo 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.DesignAssessment of baseline biomarkers using machine learning (ML) classifiers to predict tolerance to anti-VEGF therapy.ParticipantsEighty-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).MethodsA 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 evaluated using 4 ML classifiers in a cross-validated approach to distinguish between the 2 patient groups. Longitudinal assessment of changes in different texture-based radiomic descriptors (delta-texture features) between baseline and month 3 also was performed to evaluate their association with treatment response. Additionally, 8 baseline clinical parameters and a combination of baseline OCT, delta-texture features, and the clinical parameters were evaluated in a cross-validated approach in terms of association with therapeutic response.Main outcome measuresThe cross-validated area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity were calculated to validate the classifier performance.ResultsThe cross-validated AUC by the quadratic discriminant analysis classifier was 0.75 ± 0.09 using texture-based baseline OCT features. The delta-texture features within different OCT compartments between baseline and month 3 yielded an AUC of 0.78 ± 0.08. The baseline clinical parameters sub-retinal pigment epithelium volume and intraretinal fluid volume yielded an AUC of 0.62 ± 0.07. When all the baseline, delta, and clinical features were combined, a statistically significant improvement in the classifier performance (AUC, 0.81 ± 0.07) was obtained.ConclusionsRadiomic-based quantitative assessment of OCT images was shown to distinguish between super responders and non-super responders to anti-VEGF therapy in nAMD. The baseline fluid and SHRM delta-texture features were found to be most discriminating across groups.

Project description:PurposeMacular atrophy and scar increase in prevalence during treatment for neovascular age-related macular degeneration and are associated with poor visual acuity. We sought to identify the distribution of spectral-domain OCT (SD-OCT)-determined features and subretinal lesion thicknesses at sites of macular scar or atrophy after 2 years of treatment in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT).DesignCross-sectional analysis.ParticipantsCATT participants with SD-OCT, color photographic (CP) and fluorescein angiogram (FA; CP/FA) images at year 2.MethodsSixty-eight study eyes at year 2 in CATT were selected based on image quality and CP/FA-determined predominant presence of the following: geographic atrophy (GA, n = 25), non-GA (NGA, n = 44), fibrotic scar (FS, n = 26), or non-FS (NFS, n = 7). The CP/FA components were delineated by CP/FA readers; SD-OCT morphologic features and thicknesses were delineated by OCT readers. Using custom software and graphic user interfaces, images were registered, overlaying features and components per pixel; differences were analyzed across groups.Main outcome measuresOCT features, CP/FA components, and retinal and subretinal lesion thicknesses at each pixel of regional overlays.ResultsSD-OCT assessment of registered areas of pathology revealed the following: (1) retinal pigment epithelium atrophy (with or without residual lesion material) covered 75% of pixels designated as GA, 22% of NGA, 24% of NFS, and 46% of FS (P < 0.001). (2) Photoreceptor layer thinning covered 85% of GA, 42% of NGA, 33% of NFS, and 59% of FS (P < 0.001). (3) Subretinal lesion features covered 31% of GA, 42% of NGA, 85% of NFS, and 92% of FS (P < 0.001). Mean thickness of the subretinal lesion complex (measured in microns ± standard deviation) differed among GA (48±25 μm), NGA (61±35 μm), NFS (83±17 μm), and FS (151±74 μm) (P < 0.001). In eyes with GA, the thickness was greater in areas with residual lesion (51.4±27 μm) than in those without (27.2±9 μm).ConclusionsRetinal pigment epithelium atrophy and photoreceptor layer thinning are common not only in areas of macular atrophy but also in areas of FS. Photoreceptor loss extends beyond the areas of clinically apparent atrophy and FS. Subretinal lesion components were common in areas of scar, but they were also present in nearly one-third or more of areas of macular atrophy.

Project description:Intravitreal anti-vascular endothelial growth factor (VEGF) drugs have revolutionized the treatment of neovascular age-related macular degeneration (NVAMD). However, many patients suffer from incomplete response to anti-VEGF therapy (IRT), which is defined as (1) persistent (plasma) fluid exudation; (2) unresolved or new hemorrhage; (3) progressive lesion fibrosis; and/or (4) suboptimal vision recovery. The first three of these collectively comprise the problem of persistent disease activity (PDA) in spite of anti-VEGF therapy. Meanwhile, the problem of suboptimal vision recovery (SVR) is defined as a failure to achieve excellent functional visual acuity of 20/40 or better in spite of sufficient anti-VEGF treatment. Thus, incomplete response to anti-VEGF therapy, and specifically PDA and SVR, represent significant clinical unmet needs. In this review, we will explore PDA and SVR in NVAMD, characterizing the clinical manifestations and exploring the pathobiology of each. We will demonstrate that PDA occurs most frequently in NVAMD patients who develop high-flow CNV lesions with arteriolarization, in contrast to patients with capillary CNV who are highly responsive to anti-VEGF therapy. We will review investigations of experimental CNV and demonstrate that both types of CNV can be modeled in mice. We will present and consider a provocative hypothesis: formation of arteriolar CNV occurs via a distinct pathobiology, termed neovascular remodeling (NVR), wherein blood-derived macrophages infiltrate the incipient CNV lesion, recruit bone marrow-derived mesenchymal precursor cells (MPCs) from the circulation, and activate MPCs to become vascular smooth muscle cells (VSMCs) and myofibroblasts, driving the development of high-flow CNV with arteriolarization and perivascular fibrosis. In considering SVR, we will discuss the concept that limited or poor vision in spite of anti-VEGF may not be caused simply by photoreceptor degeneration but instead may be associated with photoreceptor synaptic dysfunction in the neurosensory retina overlying CNV, triggered by infiltrating blood-derived macrophages and mediated by Müller cell activation Finally, for each of PDA and SVR, we will discuss current approaches to disease management and treatment and consider novel avenues for potential future therapies.

Dataset Information

Texture-Based Radiomic SD-OCT Features Associated With Response to Anti-VEGF Therapy in a Phase III Neovascular AMD Clinical Trial.

Purpose

Methods

Results

Conclusions

Translational relevance

Publications

Texture-Based Radiomic SD-OCT Features Associated With Response to Anti-VEGF Therapy in a Phase III Neovascular AMD Clinical Trial.

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