Harpal S. Sandhu

Automatic blood vessels segmentation based on different retinal maps from OCTA scans

The retinal vascular network reflects the health of the retina, which is a useful diagnostic indicator of systemic vascular. Therefore, the segmentation of retinal blood vessels is a powerful method for diagnosing vascular diseases. This paper presents an automatic segmentation system for retinal blood vessels from Optical Coherence Tomography Angiography (OCTA) images. The system segments blood vessels from the superficial and deep retinal maps for normal and diabetic cases. Initially, we reduced the noise and improved the contrast of the OCTA images by using the Generalized Gauss-Markov random field (GGMRF) model. Secondly, we proposed a joint Markov-Gibbs random field (MGRF) model to segment the retinal blood vessels from other background tissues. It integrates both appearance and spatial models in addition to the prior probability model of OCTA images. The higher order MGRF (HO-MGRF) model in addition to the 1st-order intensity model are used to consider the spatial information in order to overcome the low contrast between vessels and other tissues. Finally, we refined the segmentation by extracting connected regions using a 2D connectivity filter. The proposed segmentation system was trained and tested on 47 data sets, which are 23 normal data sets and 24 data sets for diabetic patients. To evaluate the accuracy and robustness of the proposed segmentation framework, we used three different metrics, which are Dice similarity coefficient (DSC), absolute vessels volume difference (VVD), and area under the curve (AUC). The results on OCTA data sets (DSC=95.04±3.75%, VVD=8.51±1.49%, and AUC=95.20±1.52%) show the promise of the proposed segmentation approach.

Circular RNAs profiling in the cystathionine-β-synthase mutant mouse reveals novel gene targets for hyperhomocysteinemia induced ocular disorders

ABSTRACT Cystathionine‐&bgr;‐synthase (CBS) gene encodes L‐serine hydrolyase which catalyzes &bgr;‐reaction to condense serine with homocysteine (Hcy) by pyridoxal‐5′‐phosphate helps to form cystathionine which in turn is converted to cysteine. CBS resides at the intersection of transmethylation, transsulfuration, and remethylation pathways, thus lack of CBS fundamentally blocks Hcy degradation; an essential step in glutathione synthesis. Redox homeostasis, free‐radical detoxification and one‐carbon metabolism (Methionine‐Hcy‐Folate cycle) require CBS and its deficiency leads to hyperhomocysteinemia (HHcy) causing retinovascular thromboembolism and eye‐lens dislocation along with vascular cognitive impairment and dementia. HHcy results in retinovascular, coronary, cerebral and peripheral vessels dysfunction and how it causes metabolic dysregulation predisposing patients to serious eye conditions remains unknown. HHcy orchestrates inflammation and redox imbalance via epigenetic remodeling leading to neurovascular pathologies. Although circular RNAs (circRNAs) are dominant players regulating their parental genes expression dynamics, their importance in ocular biology has not been appreciated. Progress in gene‐centered analytics via improved microarray and bioinformatics are enabling dissection of genomic pathways however there is an acute under‐representation of circular RNAs in ocular disorders. This study undertook circRNAs analysis in the eyes of CBS deficient mice identifying a pool of 12532 circRNAs, 74 exhibited differential expression profile, ˜27% were down‐regulated while most were up‐regulated (˜73%). Findings also revealed several microRNAs that are specific to each circRNA suggesting their roles in HHcy induced ocular disorders. Further analysis of circRNAs helped identify novel parental genes that seem to influence certain eye disease phenotypes. HIGHLIGHTSCBS plays crucial roles in maintaining redox homeostasis, free‐radical detoxification and one‐carbon metabolism.CBS deficiency leads to retinovascular thromboembolism, eye‐lens dislocation, vascular cognitive impairment and dementia.CircRNAs analysis identified targets that might help in developing newer biomarkers and therapeutics for serious eye diseases.

Automated diabetic retinopathy detection using optical coherence tomography angiography: a pilot study

Background Optical coherence tomography angiography (OCTA) is increasingly being used to evaluate diabetic retinopathy, but the interpretation of OCTA remains largely subjective. The purpose of this study was to design a computer-aided diagnostic (CAD) system to diagnose non-proliferative diabetic retinopathy (NPDR) in an automated fashion using OCTA images. Methods This was a two-centre, cross-sectional study. Adults with type II diabetes mellitus (DMII) were eligible for inclusion. OCTA scans of the macula were taken, and the five vascular maps generated per eye were analysed by a novel CAD system. For the purpose of classification/diagnosis, three different local features—blood vessel density, blood vessel calibre and the size of the foveal avascular zone (FAZ)—were segmented from these images and used to train a new, automated classifier. Results One hundred and six patients with DMII were included in the study, 23 with no DR and 83 with mild NPDR. When using features of the superficial retinal map alone, the system demonstrated an accuracy of 80.0% and area under the curve (AUC) of 76.2%. Using the features of the deep retinal map alone, accuracy was 91.4% and AUC 89.2%. When data from both maps were combined, the presented CAD system demonstrated overall accuracy of 94.3%, sensitivity of 97.9%, specificity of 87.0%, area under curve (AUC) of 92.4% and dice similarity coefficient of 95.8%. Conclusion Automated diagnosis of NPDR using OCTA images is feasible and accurate. Combining this system with OCT data is a plausible next step that would likely improve its robustness.

Diagnostic Utility of Quantitative Polymerase Chain Reaction versus Culture in Endophthalmitis and Uveitis

ABSTRACT Purpose: To compare genetic testing for microbes in infectious endophthalmitis or uveitis to culture.Methods: This was a retrospective, single-center case series that enrolled patients with clinically suspected endophthalmitis or uveitis of unknown etiology. Aqueous humor or vitreous was collected and sent for routine cultures and genetic testing.Results: In total, 46 patients were enrolled. Genetic testing was positive in 32/46 (70%) cases and culture 6/46 cases (13%). Five of 16 uveitis cases had a final clinical diagnosis of infectious uveitis, and polymerase chain reaction (PCR) was positive in 4/5 cases (80%), versus 0% for culture. In uveitis cases, PCR was 80% sensitive and 82% specific, and culture had 0% sensitivity. The overall sensitivity and specificity of PCR for all cases were 85% and 67%, respectively, compared with 17% and 100% for culture.Conclusion: Genetic assays are inexpensive (

Systemic immunosuppression and risk of age-related macular degeneration

25/case) and more sensitive than culture for identifying intraocular pathogens in endophthalmitis and uveitis.

Retracted: Early diabetic retinopathy diagnosis based on local retinal blood vessels analysis in optical coherence tomography angiography (OCTA) images

A local immune response has been implicated in the pathogenesis of age-related macular degeneration (AMD), but it is unclear if systemic immunosuppressive/immunomodulatory therapy (IMT) protects against the onset and/or progression of AMD. We performed a retrospective cohort study using a Cox proportional hazards model of two cohorts. Cohort 1 included patients with stage V chronic kidney disease (CKD) status post kidney transplantation, on at least one IMT agent, and older than 50. Cohort 2 included patients with stage IV or V CKD who had not undergone kidney transplantation, were not on IMT, and were older than 50. The main outcomes were hazard ratios of a new diagnosis of dry AMD, wet AMD, or conversion from dry to wet. There were 10,813 patients in cohort 1, and 217,081 patients in cohort 2. After controlling for sex and age, there was no significant difference in the hazard of developing a new diagnosis of dry AMD (HR = 0.95, 95% CI 0.87–1.05, p = 0.32), developing a new diagnosis of wet AMD without any prior diagnosis of dry AMD (HR = 0.85, 95% CI 0.66–1.08, p = 0.18), or converting from dry to wet AMD (HR 1.24, 95% CI 0.94–1.62, p = 0.12). For patients over 70 on mycophenolate mofetil, there was a reduced hazard of converting from dry to wet AMD (HR = 0.92, 95% CI = 0.85–0.99, p = 0.02). In contrast, everolimus had an increased hazard of dry AMD (HR = 2.14, 95% CI 1.24–3.69, p < 0.01). Most systemic IMT does not affect the risk of onset or progression of AMD in patients with CKD. However, mycophenolate mofetil may confer some degree of protection against the conversion of dry AMD to wet AMD, suggesting that modulation of the immune response may prevent progression of the disease.

Automated Diagnosis and Grading of Diabetic Retinopathy Using Optical Coherence Tomography

The above article from Medical Physics, published online on 22 February 2018 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors, the journal Editor in Chief and John Wiley & Sons Ltd. The retraction has been agreed following an investigation carried out by the editors due to major overlap with a previously published article: British Journal of Ophthalmology (BJO) (Sandhu HS, Eladawi N, Elmogy M, etxa0al Automated diabetic retinopathy detection using optical coherence tomography angiography: a pilot study, British Journal of Ophthalmology Published Online First: 23 January 2018. doi:10.1136/bjophthalmol-2017-311489.

Remodeling of Retinal Architecture in Diabetic Retinopathy: Disruption of Ocular Physiology and Visual Functions by Inflammatory Gene Products and Pyroptosis

PurposenWe determine the feasibility and accuracy of a computer-assisted diagnostic (CAD) system to diagnose and grade nonproliferative diabetic retinopathy (NPDR) from optical coherence tomography (OCT) images.nnnMethodsnA cross-sectional, single-center study was done of type II diabetics who presented for routine screening and/or monitoring exams. Inclusion criteria were age 18 or older, diagnosis of diabetes mellitus type II, and clear media allowing for OCT imaging. Exclusion criteria were inability to image the macula, posterior staphylomas, proliferative diabetic retinopathy, and concurrent retinovascular disease. All patients underwent a full dilated eye exam and spectral-domain OCT of a 6 × 6 mm area of the macula in both eyes. These images then were analyzed by a novel CAD system that segments the retina into 12 layers; quantifies the reflectivity, curvature, and thickness of each layer; and ultimately uses this information to train a neural network that classifies images as either normal or having NPDR, and then further grades the level of retinopathy. A first dataset was tested by leave-one-subject-out (LOSO) methods and by 2- and 4-fold cross-validation. The system then was tested on a second, independent dataset.nnnResultsnUsing LOSO experiments on a dataset of images from 80 patients, the proposed CAD system distinguished normal from NPDR subjects with 93.8% accuracy (sensitivity = 92.5%, specificity = 95%) and achieved 97.4% correct classification between subclinical and mild/moderate DR. When tested on an independent dataset of 40 patients, the proposed system distinguished between normal and NPDR subjects with 92.5% accuracy and between subclinical and mild/moderate NPDR with 95% accuracy.nnnConclusionsnA CAD system for automated diagnosis of NPDR based on macular OCT images from type II diabetics is feasible, reliable, and accurate.

Novel therapies in the treatment of noninfectious uveitis

Diabetic patients suffer from a host of physiological abnormalities beyond just those of glucose metabolism. These abnormalities often lead to systemic inflammation via modulation of several inflammation-related genes, their respective gene products, homocysteine metabolism, and pyroptosis. The very nature of this homeostatic disruption re-sets the overall physiology of diabetics via upregulation of immune responses, enhanced retinal neovascularization, upregulation of epigenetic events, and disturbances in cells’ redox regulatory system. This altered pathophysiological milieu can lead to the development of diabetic retinopathy (DR), a debilitating vision-threatening eye condition with microvascular complications. DR is the most prevalent cause of irreversible blindness in the working-age adults throughout the world as it can lead to severe structural and functional remodeling of the retina, decreasing vision and thus diminishing the quality of life. In this manuscript, we attempt to summarize recent developments and new insights to explore the very nature of this intertwined crosstalk between components of the immune system and their metabolic orchestrations to elucidate the pathophysiology of DR. Understanding the multifaceted nature of the cellular and molecular factors that are involved in DR could reveal new targets for effective diagnostics, therapeutics, prognostics, preventive tools, and finally strategies to combat the development and progression of DR in susceptible subjects.

Expression Analysis of the Circular RNA Molecules in the Human Retinal Cells Treated with Homocysteine

ABSTRACT Introduction: Uveitis is a major cause of vision loss worldwide, and noninfectious uveitis (NIU) constitutes the majority of uveitis cases in the developed world. While corticosteroids were long the mainstays of uveitis therapy, there are now many steroid-sparing options, both systemic and local, to treat NIU. Areas covered: Herein we review the safety, efficacy, and potential clinical roles of emerging treatments for NIU beyond conventional immunosuppressive therapy and local steroid injections. These include systemic tocilizumab, an Il-6 antagonist, and new evidence regarding the anti-TNF agents adalimumab and infliximab. New local therapies to be reviewed include intravitreal methotrexate, sirolimus, and infliximab, and the dexamethasone intravitreal implant (ozurdex). A PUBMED literature review of all the agents plus the word “uveitis” was performed and all English-language articles were reviewed for the use of these agents and their mode of administration in treating noninfectious uveitis. Expert commentary: Tremendous progress has taken place in treating uveitis. The anti-TNF alpha agents have good efficacy with a reasonable safety profile. Data for intravitreal methotrexate is limited but intriguing because of its extended duration of action and limited side effects. The role of other agents is still unclear.