Dr. Sumit Sharma Profile

Dr. Sumit Sharma

at Cleveland Clinic

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Publications (2)

Proceedings Article | 15 March 2019 Paper

Morphology of vascular network in eyes with diabetic macular edema varies based on tolerance of aflibercept treatment interval length: preliminary findings

Prateek Prasanna, Justis Ehlers, Nathaniel Braman, Natalia Figueredo, Vishal Bobba, Sumit Sharma, Sunil Srivastava, Anant Madabhushi

Proceedings Volume 10953, 1095312 (2019) https://doi.org/10.1117/12.2513419

KEYWORDS: Angiography, Visualization, Tolerancing, Ischemia, Eye, Hough transforms, Medical research, Lung cancer, Blood, Capillaries

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Diabetic macular edema is a leading cause of vision loss in diabetic patients. The underlying cause for the onset of DME is 1) the long term presence of hyperglycemia and the eventual degradation of the blood-retinal barrier (BRB) via an uptick in vascular endothelial growth factor (VEGF); VEGF increases the permeability of the blood retinal barrier and alters the length of capillaries, thereby inhibiting the ability of these vessels in performing their primary function of filtration. The lack of a proper filtration system in combination with the ongoing change in intra-retinal vasculature that stems from it, results in the eventual loss of visual acuity in DME patients. Due to the large role in which VEGF plays in acting as a catalyst for the onset of DME, current treatments now focus on utilizing anti-VEGF therapy as a first line treatment for DME. Anti-VEGF therapy improves clinical outcomes in the form of improved visual acuity and reduction in macular edema. Anti-VEGF treatments also have a peripheral effect of modifying the disease burden and allowing for extended time in between treatments. However, there is still a void in understanding how anti-VEGF affects the underlying pathophysiology. This study focuses on using quantification of the geometric properties of vasculature on Fluorescein Angiography(FA) to understand the impact anti-VEGF treatment has on retinal vascular dynamics. We hypothesize that vasculature disorder, due to VEGF action, differs across patients and can be modeled mathematically to identify candidates for anti-VEGF treatment. We use VaNgOGH, a Hough transform-based descriptor to model the disorder of the retinal vascular network on baseline FA of patients subsequently treated with intravitreal anti-VEGF therapy (aibercept). VaNgOGH computes local measures of vessel-curvature and identifies dominant peaks in the accumulator space. We explored the differences in such features on baseline FA between eyes tolerating extended dosing interval (N=15) and those eyes requiring more frequent dosing (N=12), based on initial response following treatment interval extension. The cross-validated AUC was found to be 0.73±0.1 using VaNgOGH. The variance of local orientations showed a statistically significant difference (p=0.008) between the two categories, unlike clinical parameters on baseline OCT. Our results suggest there may be fundamental differences in localized vessel orientations between eyes that will exhibit favorable response to extended interval aibercept dosing and eyes that require more frequent dosing.

Proceedings Article | 15 March 2019 Paper

Spatial arrangement of leakage patterns in diabetic macular edema is associated with tolerance of aflibercept treatment interval length: preliminary findings

Prateek Prasanna, Justis Ehlers, Vishal Bobba, Natalia Figueredo, Cheng Lu, Sumit Sharma, Sunil Srivastava, Anant Madabhushi

Proceedings Volume 10953, 1095311 (2019) https://doi.org/10.1117/12.2513654

KEYWORDS: Visualization, Angiography, Tolerancing, Eye, Macula, Pathophysiology, Statistical analysis, Image segmentation, Medical research, Lung cancer

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Diabetic macular edema (DME) is a leading cause of vision loss in diabetic patients. The underlying cause for the onset of DME is the degradation of the blood-retinal barrier, whose primary function is maintaining the extracellular fluid at an optimal range. Vascular endothelial growth factor (VEGF) has proven to be a catalyst in altering the permeability of the blood-retinal barrier, thereby initiating a cascade of events that ultimately results in a loss of visual acuity.1 The primary imaging techniques to recognize and diagnose DME are fluorescein angiography (FA) and spectral-domain optical coherence tomography (SD-OCT). Taking a multimodal approach of FA in combination with SD-OCT provides images of vasculature and other eye structures to help better identify key features such as level, location, and amount of leakage.2 First-line treatments for DME have now evolved to using anti-VEGF to inhibit the effects VEGF has on increasing the permeability of the blood-retinal barrier.3 Because VEGF also increases the chance of leakage, we can also expect anti-VEGF treatments to decrease the amount of leakage DME patients suffer from. Anti-VEGF treatments also have a peripheral effect of modifying the disease burden and allowing for extended time in between treatments.4 Although current conventional treatment parameters exist to determine the efficacy of such VEGF treatments, many of these markers rely on clinicians to make a judgment call based on a minor qualitative difference of retinal scans or involve clinicians taking a fluid assessment, an option deemed too invasive to demand from all patients. In this work, we seek to find new imaging features that derive from a sub-visual feature analysis, and ideally provide a prognostic metric for clinicians to help streamline the diagnostic process. The rationale for these new biomarkers derives from leakage properties and their activity in the retina once edema develops. A decrease in leakage within certain structures in the eye would also lead to a change in the densities of leakage patterns, correlating with better clinical outcomes. In this work, we use morphological and graph-based attributes to model the global properties and spatial distribution of leakage areas on baseline FA scans of patients subsequently treated with intravitreal anti-VEGF therapy (i.e. aibercept). The features were then used in conjunction with a classifier to distinguish between eyes tolerating extended dosing intervals (N=15) and those eyes requiring more frequent dosing (N=12), based on initial response following treatment interval extension. The cross-validated area under the receiver operating characteristic curve (AUC) was found to be 0.74±0.11% using the computed imaging attributes. Edge length disorder of minimum spanning tree showed a statistically significant difference (p=0.007) between the two groups. Clinical parameters such as central subfield thickness and macular volume were not statistically significantly different. Our results indicate that there may be differences in spatial distribution of leakage areas between eyes that will exhibit favorable response to extended interval aibercept dosing and eyes that require more frequent dosing.

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