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Dive into the research topics where Dibyendu Mukherjee is active.

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Featured researches published by Dibyendu Mukherjee.


European Journal of Pharmacology | 2016

Visualization of conventional outflow tissue responses to netarsudil in living mouse eyes

Guorong Li; Dibyendu Mukherjee; Iris Navarro; Nicole Ashpole; Joseph M. Sherwood; Jinlong Chang; Darryl R. Overby; Fan Yuan; Pedro Gonzalez; Casey Kopczynski; Sina Farsiu; W. Daniel Stamer

Visual impairment due to glaucoma currently impacts 70 million people worldwide. While disease progression can be slowed or stopped with effective lowering of intraocular pressure, current medical treatments are often inadequate. Fortunately, three new classes of therapeutics that target the diseased conventional outflow tissue responsible for ocular hypertension are in the final stages of human testing. The rho kinase inhibitors have proven particularly efficacious and additive to current therapies. Unfortunately, non-contact technology that monitors the health of outflow tissue and its response to conventional outflow therapy is not available clinically. Using optical coherence tomographic (OCT) imaging and novel segmentation software, we present the first demonstration of drug effects on conventional outflow tissues in living eyes. Topical netarsudil (formerly AR-13324), a rho kinase/ norepinephrine transporter inhibitor, affected both proximal (trabecular meshwork and Schlemms Canal) and distal portions (intrascleral vessels) of the mouse conventional outflow tract. Hence, increased perfusion of outflow tissues was reliably resolved by OCT as widening of the trabecular meshwork and significant increases in cross-sectional area of Schlemms canal following netarsudil treatment. These changes occurred in conjunction with increased outflow facility, increased speckle variance intensity of outflow vessels, increased tracer deposition in conventional outflow tissues and decreased intraocular pressure. This is the first report using live imaging to show real-time drug effects on conventional outflow tissues and specifically the mechanism of action of netarsudil in mouse eyes. Advancements here pave the way for development of a clinic-friendly OCT platform for monitoring glaucoma therapy.


The Journal of Comparative Neurology | 2017

Anatomy and spatial organization of Müller glia in mouse retina

Jingjing Wang; Matthew L. O’Sullivan; Dibyendu Mukherjee; Vanessa M. Puñal; Sina Farsiu; Jeremy N. Kay

Müller glia, the most abundant glia of vertebrate retina, have an elaborate morphology characterized by a vertical stalk that spans the retina and branches in each retinal layer. Müller glia play diverse, critical roles in retinal homeostasis, which are presumably enabled by their complex anatomy. However, much remains unknown, particularly in mouse, about the anatomical arrangement of Müller cells and their arbors, and how these features arise in development. Here we use membrane‐targeted fluorescent proteins to reveal the fine structure of mouse Müller arbors. We find sublayer‐specific arbor specializations within the inner plexiform layer (IPL) that occur consistently at defined laminar locations. We then characterize Müller glia spatial patterning, revealing how individual cells collaborate to form a pan‐retinal network. Müller cells, unlike neurons, are spread across the retina with homogenous density, and their arbor sizes change little with eccentricity. Using Brainbow methods to label neighboring cells in different colors, we find that Müller glia tile retinal space with minimal overlap. The shape of their arbors is irregular but nonrandom, suggesting that local interactions between neighboring cells determine their territories. Finally, we identify a developmental window at postnatal Days 6 to 9 when Müller arbors first colonize the synaptic layers beginning in stereotyped inner plexiform layer sublaminae. Together, our study defines the anatomical arrangement of mouse Müller glia and their network in the radial and tangential planes of the retina, in development and adulthood. The local precision of Müller glia organization suggests that their morphology is sculpted by specific cell to cell interactions with neurons and each other.


Translational Vision Science & Technology | 2017

A Quantitative Approach to Predict Differential Effects of Anti-VEGF Treatment on Diffuse and Focal Leakage in Patients with Diabetic Macular Edema: A Pilot Study

Michael J. Allingham; Dibyendu Mukherjee; Erin Lally; Hossein Rabbani; Priyatham S. Mettu; Scott W. Cousins; Sina Farsiu

Purpose We use semiautomated segmentation of fluorescein angiography (FA) to determine whether anti-vascular endothelial growth factor (VEGF) treatment for diabetic macular edema (DME) differentially affects microaneurysm (MA)–associated leakage, termed focal leakage, versus non-MA–associated leakage, termed diffuse leakage. Methods We performed a retrospective study of 29 subjects treated with at least three consecutive injections of anti-VEGF agents for DME (mean 4.6 injections; range, 3–10) who underwent Heidelberg FA before and after anti-VEGF therapy. Inclusion criteria were macula center involving DME and at least 3 consecutive anti-VEGF injections. Exclusion criteria were macular edema due to cause besides DME, anti-VEGF within 3 months of initial FA, concurrent treatment for DME besides anti-VEGF, and macular photocoagulation within 1 year. At each time point, total leakage was semiautomatically segmented using a modified version of our previously published software. Microaneurysms were identified by an expert grader and leakage within a 117 μm radius of each MA was classified as focal leakage. Remaining leakage was classified as diffuse leakage. The absolute and percent changes in total, diffuse, and focal leakage were calculated for each subject. Results Mean pretreatment total leakage was 8.2 mm2 and decreased by a mean of 40.1% (P < 0.0001; 95% confidence interval [CI], [−28.6, −52.5]) following treatment. Diffuse leakage decreased by a mean of 45.5% (P < 0.0001; 95% CI, [−31.3, −59.6]) while focal leakage decreased by 17.9% (P = 0.02; 95% CI, [−1.0, −34.8]). The difference in treatment response between focal and diffuse leakage was statistically significant (P = 0.01). Conclusions Anti-VEGF treatment for DME results in decreased diffuse leakage but had relatively little effect on focal leakage as assessed by FA. This suggests that diffuse leakage may be a marker of VEGF-mediated pathobiology. Patients with predominantly focal leakage may be less responsive to anti-VEGF therapy. Translational Relevance Fluorescein angiography can define focal and diffuse subtypes of diabetic macular edema and these may respond differently to anti-VEGF treatment.


Biomedical Optics Express | 2016

Segmentation guided registration of wide field-of-view retinal optical coherence tomography volumes

José Lezama; Dibyendu Mukherjee; Ryan P. McNabb; Guillermo Sapiro; Anthony N. Kuo; Sina Farsiu

Patient motion artifacts are often visible in densely sampled or large wide field-of-view (FOV) retinal optical coherence tomography (OCT) volumes. A popular strategy for reducing motion artifacts is to capture two orthogonally oriented volumetric scans. However, due to larger volume sizes, longer acquisition times, and corresponding larger motion artifacts, the registration of wide FOV scans remains a challenging problem. In particular, gaps in data acquisition due to eye motion, such as saccades, can be significant and their modeling becomes critical for successful registration. In this article, we develop a complete computational pipeline for the automatic motion correction and accurate registration of wide FOV orthogonally scanned OCT images of the human retina. The proposed framework utilizes the retinal boundary segmentation as a guide for registration and requires only a minimal transformation of the acquired data to produce a successful registration. It includes saccade detection and correction, a custom version of the optical flow algorithm for dense lateral registration and a linear optimization approach for axial registration. Utilizing a wide FOV swept source OCT system, we acquired retinal volumes of 12 subjects and we provide qualitative and quantitative experimental results to validate the state-of-the-art effectiveness of the proposed technique. The source code corresponding to the proposed algorithm is available online.


PLOS ONE | 2018

Evaluation of inner retinal layers as biomarkers in mild cognitive impairment to moderate Alzheimer’s disease

Eleonora M. Lad; Dibyendu Mukherjee; Sandra S. Stinnett; Scott W. Cousins; Guy G. Potter; James R. Burke; Sina Farsiu; Heather E. Whitson

Inner retina in Alzheimers Disease (AD) may experience neuroinflammation resulting in atrophy. The objective of our study was to determine whether retinal GCIPL (ganglion cell-inner plexiform layer) or nerve fiber layer (NFL) thickness may serve as noninvasive biomarkers to diagnose AD. This cross-sectional case-control study enrolled 15 mild cognitive impairment (MCI) patients, 15 mild-moderate AD patients, and 18 cognitively normal adults. NFL and GCIPL thicknesses on optical coherence tomography (OCT) were measured using Duke Optical Coherence Tomography Retinal Analysis Program (DOCTRAP) and Spectralis software. We demonstrated that regional thicknesses of NFL or GCIPL on macular or nerve OCTs did not differ between groups. However, a multi-variate regression analysis identified macular areas with a significant thickening or thinning in NFL and GCIPL in MCI and AD patients. Our primary findings controvert previous reports of thinner NFL in moderate-to-severe AD. The areas of thickening of GCIPL and NFL in the macula adjacent to areas of thinning, as revealed by a more complex statistical model, suggest that NFL and GCIPL may undergo dynamic changes during AD progression.


Investigative Ophthalmology & Visual Science | 2017

Correlation Between Macular Integrity Assessment and Optical Coherence Tomography Imaging of Ellipsoid Zone in Macular Telangiectasia Type 2

Dibyendu Mukherjee; Eleonora M. Lad; Ryan R. Vann; Stephanie J. Jaffe; Traci E. Clemons; Martin Friedlander; Emily Y. Chew; Glenn J. Jaffe; Sina Farsiu

Purpose To correlate ellipsoid zone (EZ) defects on spectral-domain optical coherence tomography (SD-OCT) with retinal sensitivity loss on macular integrity assessment (MAIA) microperimetry in macular telangiectasia type 2 (MacTel). Methods Macular SD-OCT volumes and microperimetry maps were obtained during the international, multicenter, randomized phase 2 trial of ciliary neurotrophic factor for type 2 MacTel on two visits within 5 days of one another. Software was developed to register SD-OCT to MAIA scanning laser ophthalmoscopy images and to overlay EZ defect areas on the microperimetry maps generated from microperimetry sensitivity values at specific points and from interpolated sensitivity values. A total of 134 eyes of 67 patients were investigated. Results The semiautomated registration algorithm was found to be accurate, both qualitatively by visual inspection of the nearly perfect overlap of the retinal vessels and quantitatively as assessed by interobserver reliability metrics performed in 98 eyes of 49 patients (intraclass correlation of aggregate retinal sensitivity loss >0.99). Aggregate retinal sensitivity loss within the EZ defect area was highly correlated with EZ defect area (Pearson correlation coefficient 0.93 and 0.92 at screening and baseline for noninterpolated maps; both were 0.94 for interpolated maps; P values <0.001). Conclusions With our software and image processing algorithms, there is nearly perfect correlation between retinal sensitivity on microperimetry and EZ defect area on SD-OCT. Our software allows determination of functional and structural changes with increasing disease severity and demonstrates that functional loss on microperimetry may be used as a surrogate marker of EZ loss on SD-OCT in type 2 MacTel.


Proceedings of SPIE | 2016

Registration of orthogonally oriented wide-field of view OCT volumes using orientation-aware optical flow and retina segmentation(Conference Presentation)

José Lezama; Dibyendu Mukherjee; Ryan P. McNabb; Guillermo Sapiro; Joseph A. Izatt; Sina Farsiu; Anthony N. Kuo

Patient motion artifacts are an important source of data irregularities in OCT imaging. With longer duration OCT scans – as is needed for large wide field of view scans or increased scan density – motion artifacts become increasingly problematic. Strategies to mitigate these motion artifacts are then necessary to ensure OCT data integrity. A popular strategy for reducing motion artifacts in OCT images is to capture two orthogonally oriented volumetric scans containing uncorrelated motion and subsequently reconstructing a motion-free volume by combining information from both datasets. While many different variations of this registration approach have been proposed, even the most recent methods might not be suitable for wide FOV OCT scans which can be lacking in features away from the optic nerve head or arcades. To address this problem, we propose a two-stage motion correction algorithm for wide FOV OCT volumes. In the first step, X and Y axes motion is corrected by registering OCT summed voxel projections (SVPs). To achieve this, we introduce a method based on a custom variation of the dense optical flow technique which is aware of the motion free orientation of the scan. Secondly, a depth (Z axis) correction approach based on the segmentation of the retinal layer boundaries in each B-scan using graph-theory and dynamic programming is applied. This motion correction method was applied to wide field retinal OCT volumes (approximately 80° FOV) of 3 subjects with substantial reduction in motion artifacts.


Investigative Ophthalmology & Visual Science | 2016

A quantitative approach to predict differential effects of anti-VEGF treatment on diffuse and focal leakage in patients with diabetic macular edema.

Michael J. Allingham; Dibyendu Mukherjee; Erin Lally; Hossein Rabbani; Priyatham S. Mettu; Scott W. Cousins; Sina Farsiu


Investigative Ophthalmology & Visual Science | 2016

Segmentation and analysis software for mapping aqueous humor outflow pattern in living mice

Dibyendu Mukherjee; Guorong Li; W. Daniel Stamer; Sina Farsiu


Investigative Ophthalmology & Visual Science | 2016

Novel software to assess correlation between MAIA microperimetry and OCT imaging of ellipsoid zone in type 2 idiopathic macular telangiectasia

Eleonora M Lad; Dibyendu Mukherjee; Ryan R. Vann; Traci E. Clemons; Emily Y. Chew; Glenn J. Jaffe; Sina Farsiu

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Emily Y. Chew

National Institutes of Health

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