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Abstract Introduction The study aimed to evaluate comparability in terms of efficacy, safety and immunogenicity of Sun’s ranibizumab biosimilar with reference ranibizumab in patients with neovascular age-related macular degeneration (nAMD). Methods This prospective, randomised, double-blind, two-group, parallel-arm, multicentre, phase 3 comparative study included patients with nAMD ≥ 50 years, randomised (in a 2:1 ratio) in a double-blind manner to receive 0.5 mg (0.05 mL) intravitreal injection of either Sun’s ranibizumab or reference ranibizumab in the study eye every 4 weeks until week 16 (total of four doses). Results Primary endpoint results demonstrated equivalence in the proportion of patients who lost fewer than 15 letters from baseline best-corrected visual acuity (BCVA) to the end of week 16 (99% of patients in Sun’s ranibizumab and 100% in reference ranibizumab; p > 0.9999), with the proportional difference (90% confidence interval) at −1% (−2.51, +0.61) lying within a pre-specified equivalence margin. Visual acuity improved by 15 or more letters in 43% of Sun’s ranibizumab group and 37% of the reference ranibizumab group (p = 0.4267). The mean increase in BCVA was 15.7 letters in Sun’s ranibizumab group and 14.6 letters in the reference ranibizumab group (p

Bevacizumab is a monoclonal, humanized, full-length antibody targeting vascular endothelial growth factor(VEGF-A), known for its anti-angiogenic properties. The off-label use of bevacizumab has stirred legal, financial, industrial, and ethical complexities. With its potential to treat diverse ocular conditions, this commentary delves into the multifaceted dimensions of bevacizumab’s off-label utilization, encompassing clinical trials, regulatory frameworks, safety considerations, comparative effectiveness, and economic implications.

Objective Diabetic retinopathy (DR), a microvascular complication of diabetes, is a leading cause of preventable blindness. Spectral domain optical coherence tomography (SD-OCT) provides cross-sectional and topographical imaging of the retina. SD-OCT resolves outer retinal layers into three hyperreflective bands—external limiting membrane (ELM), ellipsoid zone (EZ), and retinal pigment epithelium (RPE). In this article, we have studied the role of these outer retinal layers in structural and molecular changes taking place in DR. Materials and Methods Articles with clinical features, pathogenesis, diagnosis, and treatment of DR were thoroughly studied. Articles were searched on PubMed, MEDLINE, and Cochrane Library from 2000 to 2020. Studies focusing on the role of ELM, EZ, and RPE in pathogenesis of DR based on SD-OCT were included. Results The long-standing hyperglycemia leads to protein glycosylation resulting in formation of advanced glycation end products (AGEs). AGEs have an impact through their effect on retinal microvasculature, vascular endothelial growth factor (VEGF), intercellular adhesion molecule-1, nitrosative and oxidative stress, and vitamin D and calcium metabolism. All these factors have been linked with disruption of outer retinal layers. AGEs lead to vascular endothelial dysfunction and release of proangiogenic factors by increasing the expression of VEGF in retinal pericytes and RPE cells. This leads to leakage and fluid accumulation resulting in diabetic macular edema (DME). In DME, there is sequential disruption of ELM and EZ and decrease in visual acuity (VA). The RPE alterations have been reported to be associated with the severity of DR and decrease in VA. Anti-VEGF therapy, most common treatment of DME, leads to restoration of barrier effect of ELM, it was found to be restored first followed by EZ restoration. Newer anti-AGEs agents and their receptor blockers are being developed which have a positive effect on maintaining the health of RPE. Conclusion A complex molecular association exists between the structural changes in ELM, EZ, and RPE in DR. SD-OCT is an indispensable tool to study these changes as integrity of these outer layers of retina is essential for maintaining visual function of retina in DR.

One of the most significant challenges facing the healthcare industry in the digital age is interoperability. At the present, electronic health records (EHRs) including the medical history of the patient, laboratory tests, demographics, medication and allergies, immunization status, radiology images, vital signs all are hidden in isolated databases, incompatible systems and proprietary software, which creates biggest obstacles to data exchange, analyze, and interpret. Healthcare sector is realizing the thrust of a system which allows healthcare facilities to access, analyze, and enhanced communication between systems, medical devices, and applications at a local or cross-organizational level. Application Programming Interface (API) integration has become the most popular solution for managing the flow of data between internal applications, EHRs, and other data exchange tools in the healthcare industry by enabling applications to exchange data and functionality easily and securely. In this paper, we suggest that interoperability is a must for most of the upcoming medical advancements. Among various examples of emerging technologies like IoT, SaaS and cloud computing, APIs are the best tool in order to maximize the performance in terms of earning more income, better understanding their customers, etc. The paper highlights the benefits of API and suggests a framework of API led integration to improve the interoperability of patient health information between healthcare organizations while maintaining the privacy and security of data.

Objectives: To determine the prevalence and predictors of Retinopathy of prematurity (ROP) and severe ROP. Methods: A prospective observational study (April 2019–May 2020) was conducted at a tertiary care center in preterm newborns with; 1) birth-weight

Abstract E2F1 induces hundreds of protein-coding genes influencing diverse signaling pathways but much less is known about its non-coding RNA targets. For identifying E2F1-dependent oncogenic long non-coding RNAs (lncRNAs), we carried out genome-wide transcriptome analysis and discovered an lncRNA, EMSLR, which is induced both in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). EMSLR depletion blocks the cells in G1 phase and inhibits the clonogenic ability indicating that it is essential for the tumor-related phenotypes. We discovered that EMSLR represses the promoter activity of another lncRNA, LncPRESS1, which is located 6.9 kb upstream of EMSLR and they display an inverse expression pattern in lung cancer cell lines. Depletion of C-MYC results in downregulation of EMSLR and simultaneous upregulation of EMSLR target LncPRESS1, exemplifying how C-MYC and E2F1 signal transduction pathways control the network of lncRNA genes to modulate cell proliferation and differentiation.

Abstract Background Razumab™ (world’s first biosimilar ranibizumab) is approved for several macular disorders including wet age-related macular degeneration (AMD). We evaluated the safety and efficacy of biosimilar ranibizumab in wet AMD. Methods This prospective, multicentre, rAnibizumab bioSimilar Safety Efficacy postmarkeTing (ASSET) study enrolled patients aged ≥ 50 years with wet AMD having best-corrected visual acuity (BCVA) between 20/40 and 20/320. The patients received intravitreal biosimilar ranibizumab 0.5 mg every 4 weeks for 24 weeks. Safety endpoints included the incidence of adverse events (AEs), serious AEs (SAEs), and immunoreactivity after 6 months. The efficacy endpoints were the proportion of patients who lose fewer than 15 letters, increase in BCVA, change in central retinal thickness (CRT), and change in Visual Function Questionnaire-25 (VFQ-25) score, from baseline to 24 weeks. Results Of the 126 enrolled patients, majority (95.24%) of the patients received all 6 doses of biosimilar ranibizumab (total 3 mg). Nineteen AEs were reported (n = 16; 12.7%); majority (78.9%) were mild. There were no serious AEs reported, except one AE of death which was unrelated to the study drug. None of the patients discontinued the study due to an AE. The most common ocular AE was increase in intraocular pressure (4 events) and non-ocular AE was pyrexia (5 events). A total of 7.9% (10/126) patients prior to dosing and 7.1% (9/126) patients post-treatment were positive for anti-ranibizumab antibodies. No AEs suggestive of immunogenicity were noted. At 24-weeks, 97.60% patients in the intent-to-treat (ITT) population (N = 125) and 97.41% patients in the per-protocol (PP) population (N = 116) lost

Blockchain- and smart-contract technology enhance the effectiveness and automation of business processes. The rising interest in the development of decentralized autonomous organizations (DAO) shows that blockchain technology has the potential to reform business and society. A DAO is an organization wherein business rules are encoded in smart-contract programs that are executed when specified rules are met. The contractual- and business semantics are sine qua non for drafting a legally-binding smart contract in DAO collaborations. Several smart-contract languages (SCLs) exist, such as SPESC, or Symboleo to specify a legally-binding contract. However, their primary focus is on designing and developing smart contracts with the cooperation of IT- and non-IT users. Therefore, this paper fills a gap in the state of the art by specifying a smart-legal-contract markup language (SLCML) for legal- and business constructs to draft a legally-binding DAO. To achieve the paper objective, we first present a formal SCL ontology to describe the legal- and business semantics of a DAO. Secondly, we translate the SCL ontology into SLCML, for which we present the XML schema definition. We demonstrate and evaluate our SLCML language through the specification of a real life-inspired Sale-of-Goods contract. Finally, the SLCML use-case code is translated into Solidity to demonstrate its feasibility for blockchain platform implementations.

Abstract Advances in spectral-domain optical coherence tomography (SD-OCT) technology have enhanced the understanding of external limiting membrane (ELM) and ellipsoid zone (EZ) in diabetic macular edema. An increase in VEGF has been demonstrated to be associated with sequential ELM and EZ disruption on SD-OCT. An intact ELM is a prerequisite for an intact EZ in DME. Anti-VEGF therapy leads to restoration of barrier effect of ELM. The ELM restores first followed by EZ restoration.

Abstract Background The present study was undertaken to assess the resistive index (RI) of central retinal artery (CRA) as a bioimaging biomarker for the severity of diabetic retinopathy (DR), for the first time. Methods Eighty-one consecutive patients of type 2 diabetes mellitus between the ages of 40 and 70 years were included in a tertiary care center-based cross sectional study. Severity of retinopathy was assessed according to Early Treatment Diabetic Retinopathy Study (ETDRS) classification: diabetes mellitus with no retinopathy (No DR) (n = 26); non-proliferative diabetic retinopathy (NPDR) (n = 29); and proliferative diabetic retinopathy (PDR) (n = 26). Twenty-six healthy controls of similar age were also included. Resistive index of CRA was studied using color Doppler and gray scale sonography. Central subfield thickness (CST), cube average thickness (CAT), retinal photoreceptor ellipsoid zone (EZ) disruption, and retinal nerve fiber layer (RNFL) thickness were evaluated using spectral domain optical coherence tomography. Sensitivity and specificity were assessed by receiver operating characteristic (ROC) curve. Results Mean RI of CRA for the study groups revealed significant increase with severity of diabetic retinopathy (F = 10.24, P

Abstract Background Vitamin D is a multi-functional fat-soluble metabolite essential for a vast number of physiological processes. Non-classical functions are gaining attention because of the close association of vitamin D deficiency with diabetes, and its complications. The present study was undertaken to evaluate the role of vitamin D as a biomarker for proliferative diabetic retinopathy. Methods A tertiary care center based cross-sectional study was undertaken. Seventy-two consecutive cases of type 2 diabetes mellitus were included. Diagnosis of diabetes mellitus was made using American Diabetes Association guidelines. Study subjects included: diabetes mellitus with no retinopathy (No DR) (n = 24); non-proliferative diabetic retinopathy (n = 24); and proliferative diabetic retinopathy (n = 24) and healthy controls (n = 24). All of the study subjects underwent complete ophthalmological evaluation. Best Corrected Visual Acuity (BCVA) was measured on the logarithm of the minimum angle of resolution (logMAR) scale. Serum 25-OH Vitamin D assay was done using chemiluminescent microparticle immunoassay technology. Diagnostic accuracy of vitamin D was assessed using receiver operating characteristics curve analysis and area under curve (AUC) was determined for the first time. Results ANOVA revealed a significant decrease in serum vitamin D levels with severity of diabetic retinopathy (F = 8.95, p

Abstract Background Elevated serum vascular endothelial growth factor (VEGF) levels are associated with diabetic retinopathy (DR). Serum VEGF levels correlate with vitreous levels. Neuroretinal changes occur even before the appearance of vascular signs in DR. Role of VEGF as a biomarker for DR has not been assessed. Serum VEGF as a biomarker for severity of DR, was evaluated for the first time. Methods Consecutive cases of type 2 diabetes mellitus [without DR, (no DR, n = 38); non-proliferative DR, (NPDR, n = 38); proliferative DR, (PDR, n = 40)] and healthy controls (n = 40) were included. Serum VEGF was measured using enzyme linked immunosorbent assay. Accuracy of VEGF as a biomarker for severity of retinopathy was measured using the area under the receiver operator characteristic (ROC) curve. Results Serum VEGF levels in controls, No DR, NPDR and PDR groups showed significant incremental trend from 138.96 ± 63.37 pg/ml (controls) to 457.18 ± 165.69 pg/ml (PDR) (F = 48.47; p

In regenerative animals, how cells respond to injury signals inducing senescence is unclear. Here, the authors show that cells from highly regenerative mammals are resistant to ROS-induced cellular senescence, but non-regenerating species exhibit mitochondrial dysfunction/senescence in response to hydrogen peroxide exposure.

Abstract A paracentesis prior to an intravitreal injection is a very safe procedure and can prevent IOP-spikes after injections. As these spikes pose the risk of inducing glaucomatous changes particularly in patients with frequent injections and/or with a risk profile, a regular paracentesis prior to an injection may be considered and discussed with the patient.

COVID-19 is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and has been shown to affect a multitude of organ systems. It is often associated with vasculitis or thromboembolic disease with resultant tissue hypoxia. This report presents a case of fast progression diabetic retinopathy in the case of a SARS-CoV-2 infection. The findings conclude that patients with diabetes should be more frequently monitored for emergence or progression of diabetic retinopathy if they present with COVID-19.

Abstract Background To evaluate the association of central subfield thickness (CST) and cube average thickness (CAT) with ellipsoid zone (EZ) disruption on spectral domain optical coherence tomography (SD-OCT) in patients of diabetic retinopathy (DR). Methods Cross sectional study including consecutive patients of type 2 diabetes mellitus [without DR (No DR, n = 97); non-proliferative DR (NPDR, n = 91); proliferative DR (PDR, n = 83)] and healthy controls (n = 82) was undertaken. CST and CAT values were measured using SD-OCT. Data was analyzed using Chi square test, ANOVA and multivariate analysis. Discriminant values of CST and CAT for EZ disruption were evaluated using receiver operator characteristic curve. Area under curve (AUC) was computed. Results Mean CAT and CST values in the study subjects showed an incremental trend. Multivariate ordinal logistic regression analysis showed increase in CST (OR = 1.022, p

Abstract Background Retinal pigment epithelium (RPE) plays a significant role in maintenance of integrity of retinal photoreceptors and choriocapillaries. RPE derives its blood supply through ophthalmic artery (OA) via choriocapillaries. RPE topographic alterations have been observed to be associated with severity of retinopathy. The present study was undertaken to assess the correlation between resistive index (RI) of the OA with RPE topographic alterations on Spectral-Domain optical coherence tomography (SD-OCT), to our knowledge, it is for the first time. Methods A tertiary care center based cross-sectional study was undertaken after informed consent. Sample size was calculated using 95% confidence interval. Seventy five consecutive cases of type 2 diabetes mellitus between the ages of 40 and 70 years were included. The cases were divided into three groups according to Early Treatment Diabetic Retinopathy Study classification: diabetes mellitus with no retinopathy (No DR) (n = 24); non-proliferative diabetic retinopathy (n = 27); and proliferative diabetic retinopathy (n = 24). Healthy control subjects of similar age group were included (n = 24). RI in OA was studied using Color Doppler imaging. Grades of RPE topographic alterations and retinal photoreceptor ellipsoid zone (EZ) disruption were studied using SD-OCT. Data was analysed using Chi square (χ2) test, analysis of variance (ANOVA), Pearson correlation analysis and Neuman–Keuls test. Results LogMAR best corrected visual acuity was found to increase significantly with the severity of DR (F = 105.74, p

AIM: To evaluate retinal nerve fiber layer (RNFL) thickness profile in patients of thyroid ophthalmopathy with no clinical signs of optic nerve dysfunction. METHODS: A prospective, case-control, observational study conducted at a tertiary care centre. Inclusion criteria consisted of patients with eyelid retraction in association with any one of: biochemical thyroid dysfunction, exophthalmos, or extraocular muscle involvement; or thyroid dysfunction in association with either exophthalmos or extra-ocular muscle involvement; or a clinical activity score (CAS)>3/7. Two measurements of RNFL thickness were done for each eye, by Cirrus HD-optical coherence tomography 6mo apart. RESULTS: Mean age of the sample was 38.75y (range 13-70y) with 18 males and 22 females. Average RNFL thickness at first visit was 92.06±12.44 µm, significantly lower than control group (101.28±6.64 µm) (P=0.0001). Thickness of inferior quadrant decreased from 118.2±21.27 µm to 115.0±22.27 µm after 6mo (P=0.02). There was no correlation between the change in CAS and RNFL thickness. CONCLUSION: Decreased RNFL thickness is an important feature of thyroid orbitopathy, which is an inherent outcome of compressive optic neuropathy of any etiology. Subclinical RNFL damage continues in the absence of clinical activity of the disease. RNFL evaluation is essential in Grave’s disease and active intervention may be warranted in the presence of significant damage.

Introduction: Various cross-sectional studies indicate that dyslipidemia and increased activity of enzyme Aldose Reductase (ALDR-2) are associated with the establishment of Diabetic Retinopathy (DR). However, it remains unclear that among dyslipidemia and ALDR-2 activity, which is more important for the progression of DR from nonproliferative to the proliferative stage. Aim: The present study was designed to explore the role of dyslipidemia and ALDR-2 activity in the progression of DR. Materials and Methods: Two hundred subjects were involved in this cross-sectional study, 150 subjects had Type 2 diabetes while 50 had No Diabetes and No Retinopathy (NDNR) and acted as controls. On the basis of fundus examination, diabetic subjects were further divided equally into those having: No Retinopathy (DNR), Non-Proliferative DR (NPDR), and Proliferative DR (PDR). Fasting lipid profile, ALDR-2 level, fasting and postprandial blood sugar were measured using a standard protocol. Data were analysed using both descriptive and inferential statistics using unpaired t-test. Results: ALDR-2 level was significantly (p-value=0.0001) higher in NPDR than DNR. Low-Density Lipoprotein Cholesterol (LDL-C) was significantly (p-value=0.0235) higher in PDR than NPDR. Fasting Blood Sugar (FBS), Postprandial Blood Sugar (PPS), and LDL-C were significantly higher in DNR than NDNR while high-density lipoprotein cholesterol was significantly lower in DNR than NDNR group. Conclusion: Persistent hyperglycaemia causes an increased ALDR-2 activity that has a significant role in the establishment of DR. However, dyslipidemia is more important as a risk factor for progression of NPDR to PDR. Hypolipidemic drug as an adjunctive therapy could prevent the progression of DR from NPDR to PDR.

In current study two important proteins of Eales' disease, i.e. Retinal S-antigen (RSAG) (P10523) and Retinol binding protein-3 (RBP-3) (P10745), retrieved from Swiss prot database, are analysed and characterized through in silico tools. Characterization is carried out in terms of molecular weight, atomic composition, isoelectric point, extinction coefficient, aliphatic index and instability index. Primary structure analysis of target proteins showed that most of the amino acids are hydrophobic in nature which was evident due to the high content of non-polar residues. Thermal stability, which is a notification regarding the flexibility in the structure of protein, is higher here, i.e. 88.27 for RSAG and 100.31 of RBP-3 suggesting their stability in a wide range of temperature. Secondary structure analysis of RBP-3 and RSAG reveals that RBP-3 mostly have alpha helices while RSAG have mixed secondary structures, i.e. the alpha helices, extended strands and random coils which is suggestive about the high structural conservity of protein. This evolutionary conservity makes RSAG a better target against Eales' disorder. Determination of phosphorylation as well as signal peptide cleavage sites is another integral part of in silico characterization, as these determinations confirms about the functional aspect of protein.

Anxiety and depression are major chronic mood disorders, and the etiopathology for each appears to be repeated exposure to diverse unpredictable stress factors. Most of the studies on anxiety and related mood disorders are performed in rodents, and a good model is chronic unpredictable stress (CUS). In this study, we have attempted to understand the molecular basis of the neuroglial and behavioral changes underlying CUS-induced mood disorders in the simplest vertebrate model, the zebrafish, Danio rerio. Zebrafish were subjected to a CUS paradigm in which two different stressors were used daily for 15 days, and thorough behavioral analyses were performed to assess anxiety and related mood disorder phenotypes using the novel tank test, shoal cohesion and scototaxis. Fifteen days of exposure to chronic stressors appears to induce an anxiety and related mood disorder phenotype. Decreased neurogenesis, another hallmark of anxiety and related disorders in rodents, was also observed in this zebrafish model. The common molecular markers of rodent anxiety and related disorders, corticotropin-releasing factor (CRF), calcineurin (ppp3r1a) and phospho cyclic AMP response element binding protein (pCREB), were also replicated in the fish model. Finally, using 2DE FTMS/ITMSMS proteomics analyses, 18 proteins were found to be deregulated in zebrafish anxiety and related disorders. The most affected process was mitochondrial function, 4 of the 18 differentially regulated proteins were mitochondrial proteins: PHB2, SLC25A5, VDAC3 and IDH2, as reported in rodent and clinical samples. Thus, the zebrafish CUS model and proteomics can facilitate not only uncovering new molecular targets of anxiety and related mood disorders but also the routine screening of compounds for drug development.