bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extraneous factors affecting retinal oximetry
Authors: HUDSON C , PATEL SR , SHAHIDI AM , KULASEKARA S , FLANAGAN JG 
Published: August 2012

AbstractPurpose To identify extraneous factors that can impact the outcome of retinal oximetry calculations and to discuss how these factors might be negated.Methods 1. Empiric observation of extraneous factors suspected to impact the outcome of retinal oximetry. 2. Controlled studies of established and suspected extraneous factors.Results 1. The repeatability of a manual oximetry technique was found to be good. The standard deviations of Optical Density (OD) values ranged from 0.01 to 0.06 OD units and from 0.01 to 0.07 OD units for first degree arterioles and venules, respectively. The Co‐efficient of Repeatability (CoR) ranged from 0.02 to 0.11 OD units (relative to a mean OD of 0.15 [0.06‐0.23] OD units) for arterioles and 0.03 to 0.14 OD units (relative to a mean OD of 0.25 [0.17‐0.31] OD units) for venules. Good reliability (p<0.001) was found for arterioles and venules. 2. Dual ratiometric calculations of retinal oxygen saturation (SO2) demonstrated a significant decrease of arterial SO2 during hypoxia. 3. The order of acquisition of spectral images did not influence the outcome of retinal oximetry results. 4. The manual calculation of SO2 values from reflectance data was significantly influenced by the selected retinal locations within and either side of a given retinal vessel. Other extraneous factors included: 5. Variation in retinal pigmentation; 6. Density of retinal pigmentation); 7. Instrument flash intensity; 8. Lenticular irregularities; 9. Tear film irregularities.Conclusion Although the assessment of retinal SO2 in ocular diseases would seem to be of clinical value, a number of extraneous factors must first be taken into account to avoid erroneous conclusions.
Commercial interest
Clinical aspects of retinal oximetry
Authors: GIBSON J 
Published: August 2012

AbstractPurpose To review the current and future role of retinal oximetry in the clinical management of retinal disorders.Methods By review of the published literature.Results Examples of retinal oximetry use in retinal and retinovascular disorders will be presented.Conclusion In the age of widespread use of anti‐VEGF agents in retinal disorders, retinal imaging has become paramount for the treating ophthalmologist. Retinal oximetry enables retinal imaging to be coupled with an assessment of metabolic function of the retina and this may permit more targeted therapies to be given.
Novel therapeutic targets in diabetic retinopathy
Authors: SCHLINGEMANN RO 
Published: August 2012

AbstractThe present armatorium for the prevention or treatment of diabetic retinopathy (DR) comprises modulation of systemic factors, laser, surgical approaches, anti‐VEGF agents and corticosteroids. In designing new therapies, the clinical targets of the various stages of DR should be clearly defined: these are vasoregression in pre‐clinical DR, blood‐retinal barrier loss, inflammation and retinal ischemia in macular edema, and angiogenesis and fibrosis in proliferative DR. With regards to early vasoregression, glucose‐induced alterations in biochemical pathways, growth factors such as CTGF and Angiopoeitin‐2, and leukocyte adhesion are under investigation as targets for prevention, whereas stem cell approaches have been suggested to allow repair of already degenerated retinal capillaries. For non‐proliferative DR and macular edema, inflammatory targets such as TNF‐alpha, IL‐6, IL‐10 and the Kallikrein‐Kinin system are under investigation as targets for alternative or adjunct treatments for anti‐VEGF and laser. However, the growing understanding of the cellular mechanisms of blood‐retinal barrier loss may also allow for more directed therapies aimed at the paracellular or transcellular pathways of leakage, while new neuroprotective agents may restrict the ongoing neuronal loss in this stage of DR. For inhibition of angiogenesis in proliferative DR, several novel agents are available to enter clinical development. Finally, recent new insights in the pathogenesis of the angio‐fibrotic switch and scarring have identified CTGF and other factors as potential therapeutic targets for prevention of this final blinding phase of DR.
Investigator‐initiated trials: a corporate perspective
Authors: LAMBROU G 
Published: August 2012

AbstractThe scope, size and regulatory sponsor requirements for Clinical Trials related to Medicinal Products have reached, over the past two decades, a degree of complexity making them increasingly difficult to implement by non‐industrial sponsors. In recent years, however, these difficulties are being recognized, and various initiatives and guidelines to facilitate Investigator‐Driven Clinical Trials indicate that the situation may be gradually changing. Novartis recognizes that scientifically rigorous Investigator‐Initiated Trials with a sound medical rationale can provide essential contributions in furthering knowledge about diseases and their treatments. It therefore encourages implementation by the Healthcare Community of meaningful Clinical Research that adds to better understanding of medical needs and how to address them, with the ultimate purpose of optimizing patient care and treatment outcomes. In this presentation the concept of Investigator‐Initiated Trials will be discussed from an industry perspective. The regulatory guidelines and Novartis processes for supporting such trials will be explained, using examples from the field of Ophthalmology, and the potential areas of interest in Retinal Vascular Diseases will be outlined.
Identifying progression of retinal disease in eyes with NPDR in diabetes type 2 using non‐invasive procedures. Protocol nº ECR‐RET‐2010‐02. ClinicalTrials.gov Identifier: NCT01145599
Authors: CUNHA‐VAZ J 
Published: August 2012

AbstractPurpose To identify eyes that show worsening and disease progression (progressor phenotypes)Methods To identify Diabetic Retinopathy “progressors” to clinically significant retinal edema in type 2 diabetic patients with early NPDR, from baseline to the 12‐month visit, assessed by biomarkers. Primary Outcomes: Microaneurysms turnover computed from color fundus photographs using the RetmarkerDR software; Retinal thickness increase in the central subfield. Secondary Outcomes: BCVA changes; ETDRS step changes; and rescue treatment.Results Observational study with a follow‐up at 0, 3, 6 and 12 months in eyes with NPDR (≤35). Color fundus photographs analyzed with the RetmarkerDR software for automated assessment of microaneurysms turnover (MA formation and disappearance rate). Retinal thickness measured with Frequency Domain Optical Coherence Tomography (FD‐OCT).
Prospective, randomized, multicenter, open label, phase II / III study to assess efficacy and safety of ranibizumab 0.5 mg intravitreal injections plus panretinal photocoagulation (PRP) versus and PRP in monotherapy in the treatment of patients with high risk proliferative diabetic retinopathy. PROTEUS
Authors: FIGUEIRA J 
Published: August 2012

AbstractPurpose To compare efficacy and evaluate safety of intravitreal (ITV) injection of ranibizumab (0.5 mg) plus PRP versus PRP alone in the regression of retinal neovascularization (NV) in eyes with high‐risk proliferative diabetic retinopathy (HR‐PDR).Methods Primary Outcome: Regression of neovascularization (NV). Secondary Outcomes: 1) Best‐Corrected Visual Acuity (BCVA) loss – changes from baseline; 2) Time to NV regression; 3) Recurrence of neovascularization; 4) Macular retinal thickness by Optical Coherent Tomography (OCT) – changes from baseline; 5) Laser needed for Diabetic Macular Edema (DME); 6) Vitrectomy needed due to the occurrence of vitreous hemorrhage or retinal detachment; 7) Drug safety profile.Results This is a prospective, randomized, multicenter, open label, phase II / III study to assess efficacy and safety of ranibizumab plus PRP versus PRP alone in the treatment of subjects with HR‐PDR. Number Patients: 94 eyes from 94 diabetic patients: Randomized 1:1; Group 1: 47 eyes (PRP group); Group 2: 47 (ranibizumab + PRP).
Inflammasome activation by oxidative stress in ARPE‐19 cells
Authors: KAUPPINEN A , LAAKSO N , KINNUNEN K , SALMINEN A , KAARNIRANTA K 
Published: August 2012

AbstractPurpose It is known that oxidative stress and inflammation are associated with the age‐related macular degeneration (AMD). Retinal pigment epithelial (RPE) cells are responsible for the immune defense of retina, and they are constantly exposed to oxidative stress, a condition where the amount of intracellular oxidizing agents becomes increased with a concurrent decline in the cell´s defensive systems. Inflammasomes are intracellular protein complexes which become activated by danger signals encountered by the cell. They play a major role in innate immunity responses but their detailed contribution has still largely remained to be elucidated. In the present study, we have examined the association of oxidative stress with the inflammasome activation in human ARPE‐19 cells.Methods The cells were pre‐treated or not treated with the bacterial endotoxin LPS, and thereafter exposed to the lipid peroxidation end product 4‐hydroxynonenal (HNE).Results Our data show that HNE significantly increased the production of proinfammatory cytokines IL‐1beta and IL‐18 but LPS by itself did not. Pretreatment of the cells with LPS, however, further enhanced the HNE‐stimulated cytokine production. PCR analysis revealed that HNE induced a significant increase in the amount of the receptor component NLRP3 mRNA compared to control cells. The amount of NLRP1 mRNA remained unchanged.Conclusion Our results suggest that LPS provided the first signal needed for the inflammasome activation. Thereafter, HNE triggered the assembly of the NLRP3 inflammasome complex.
IL‐17A as a possible target of anti‐inflammatory and anti‐parasitic treatment in toxoplasmic uveitis
Authors: SAUER A , PFAFF A , CREUZOT‐GARCHER C , DALLE F , CHIQUET C , PELLOUX H , SPEEG‐SCHATZ C , CANDOLFI E , BOURCIER T 
Published: August 2012

AbstractPurpose Toxoplasmosis is the most common cause of posterior uveitis in immunocompetent subjects. Taking into account the opposing needs of limiting parasite multiplication and minimizing tissue destruction, the immune imbalance implies especially Th17 and T regulatory (Treg) cells.Methods In a multicenter prospective clinical study of intraocular inflammation (PHRC 3964), we evaluated the cytokine pattern in aqueous humors of 10 T. gondii infected patients. To determine the immunological mechanisms, we evaluated intraocular inflammation, parasite load, and immunological responses using mRNA and protein levels in a mouse model. Anti‐IL‐17A monoclonal antibodies (mAbs) were administered with the parasite in order to evaluate the role of IL‐17A.Results We observed severe ocular inflammation and cytokine patterns comparable to human cases, including IL‐17A production. Neutralizing IL‐17A decreased intraocular inflammation and parasite load in mice. Detailed studies revealed upregulation of Treg and Th1 pathways. When IFN‐γ was neutralized concomitantly, the initial parasite multiplication rate was partially restored.Conclusion Local IL‐17A production by resident cells plays a central role in the pathology of OT. The balance between Th17 and Th1 responses (especially IFN‐γ) is crucial for the outcome of infection. This data reveals new in vivo therapeutic approaches by repressing inflammatory pathways using intravitreal injection of IL‐17A mAbs.
Intracranial pressure and glaucoma
Authors: JONAS JB 
Published: August 2012

AbstractPurpose There are facts and myths. The fact is, that the orbital cerebrospinal fluid pressure (CSF‐P) is the real counter‐pressure against the intraocular pressure across the lamina cribrosa. The myth is that an abnormally low orbital CSF‐P is involved in the pathogensis of normal‐(IOP)pressure glaucoma.Methods The talk will present the results of recent studies which may shed some light on the question wherther CSF‐P is related to glaucoma
Autonomic nervous system dysfunction in glaucoma
Authors: GHERGHEL DOINA 
Published: August 2012

AbstractAlthough abnormal intraocular pressure (IOP) is the main risk factor for the development of primary open‐angle glaucoma (POAG), other culprits including ocular microvascular dysregulation and systemic vascular abnormalities have been implicated in its etiology. The status of autonomic nervous system (ANS) is an important determinant of the systemic hemodynamic parameters implicated in glaucoma pathogenesis. Nevertheless, assessing the ANS function is not a practice in glaucoma diagnosis and management. Consequently, there is a lack of alternative therapies tailored to address associated systemic risk factors for POAG on a case and chronological wise basis; this approach could possibly be more effective in preventing the progression and visual loss in selected glaucoma cases.
Retinal vessel analysis and oximetry ‐ technical advances and clinical applications
Authors: HAMMER M 
Published: August 2012

AbstractPurpose To develop and evaluate a method for simultaneous measurements of retinal vessel oxygen saturation and vessel diameter change upon flicker light stimulation.Methods Dual – wavelength (548 nm and 610 nm) fundus images were taken before (baseline) and during luminance flicker stimulation (12.5 Hz, modulation depth: 1:25). Retinal vessel oxygen saturation (OS, dual – wavelength optical oximetry) and diameters (central retinal arterial and venous equivalents – CRAE and CRVE) were determined. Investigations were performed in 19 healthy volunteers (mean age: 26 ± 2.5 years), 18 patients with diabetic retinopathy (62.2±8.3 years), 16 glaucoma patients with IOP (≤22 mmHg, mean 16±3.5 mmHg, mean age 66±14 year), and 20 age matched controls (71.2±7.5 years).Results In the young population, the flicker increased CRAE, CRVE, and venous OS statistically significant from 193 ± 20 µm, 228 ± 20 µm, and 60 ± 5.7% at baseline to 202 ± 19 µm, 242 ± 17 µm, and64 ± 5.9% (all p<0.0005).. Flicker light increased CRAE, CRVE, and venous OS by 1.42%±3.72%, 2.80%*±2.70%, and 2.03%*±2.43% in the patients as well as 4.98%*±6.23%, 8.94%*±5.26%, and 4.20%*±3.71% in the controls (*: p<0.05). Also in glaucoma patients, the increase of venous OS upon flicker was smaller in the patients than in the controls (1.9±4.9%).Conclusion Oxygen supply or consumption is reduced in diabetic retinopathy as well as glaucoma. The simultaneous measurements of retinal vessel oxygen saturation and vessel diameter change upon flicker light stimulation should be considered for the investigation of such impairment of oxygen supply.
Commercial interest
Genetic analyses of uveal melanoma metastases
Authors: SAULE S , COUTURIER J , STERN MH , MARIANI P , DESJARDINS L , ROMAN‐ROMAN S , BARILLOT E , PIPERNO‐NEUMANN S , LAURENT C 
Published: August 2012

AbstractPurpose To identify genes linked to metastasis development in uveal melanoma (UM), transcriptome analysis linked to comparative genomic hybridization was performed with 63 primary tumors and 115 liver metastasis. 9 primary tumors and their matched metastasis (couples) were also analyzed. A biostatistical approach was used to define the genetic prognosis parameters. BAP‐1 mutations reported to be frequently present in class 2 UM were investigated.Results Fifteen percent of the metastases were found disomic for the chromosome 3 (suggesting a class1 profile) and the couples were monosomic for chromosome 3 (suggesting a class2 profile). Examination of the genomic imbalances in couples (all with monosomy 3, suggesting a class2 profile) indicated that no major alterations occurred at the metastatic step. Very few genes (30) were found differentially expressed between the primary tumor and the metastasis after removal of liver expressed genes.Conclusion These results suggest that the events leading to the metastasis spreading are already present in the primary tumor.
Prediction of metastasis
Authors: DAMATO B , COUPLAND SE 
Published: August 2012

AbstractPurpose To describe the Liverpool approach to the prediction of metastasis from uveal melanoma.Methods The Liverpool Ocular Oncology Research Group (LOORG) has developed the Liverpool Uveal Melanoma Prognosticator Online (LUMPO), which is available free on the internet at www.ocularmelanomaonline.com. This estimates the survival probability according to age, sex, largest basal tumour diameter, tumour thickness, ciliary body involvement, extraocular spread, melanoma cytomorphology, mitotic count, extravascular matrix pattern and chromosome 3 status. An all‐cause survival curve is generated using the accelerated failure time mathematical model. A survival curve for the general British population of the same age and sex is also generated. By subtracting one curve from the other it is possible to estimate metastatic mortality.Results LUMPO has been developed with data on more than 3000 patients and has been thoroughly validated. The results depend greatly on the accuracy of clinical measurements, mitotic counts and genetic typing. We have found FISH to be inadequate and have replaced this with MLPA and MSA, reserving the latter for small biopsy samples. Biopsy techniques have also improved and these have enhanced the results of prognostication.Conclusion With advances in biopsy, genetic testing and multivariate analysis, we are now able to provide personalised prognostication. This enhances the quality of life of patients with a good prognosis while enabling us to target intensive care,such as counselling and screening, at high‐risk patients. Improved prognostication has also enhances opportunities for basic science research, facilitating the identification of molecular abnormalities influencing the metastatic process.
Serum biomarkers of metastatic disease: current practice and future perspectives
Authors: ANGI M , KALIRAI H , DAMATO B , COUPLAND SE 
Published: August 2012

AbstractPurpose Molecular genetic testing of primary uveal melanoma (UM) specimens is being integrated into clinical practice for prognostication purposes. However, the current screening protocol for metastatic disease (MD) it is not able to detect micrometastases. There is a clear need for easily assessable biomarkers that would allow earlier detection of MD and aid monitoring of systemic adjuvant therapy. As UM disseminates haematogeneously, it is reasonable to search for blood‐borne biomarkers as indicators of MD.Methods Review of the literature to provide an overview of blood biomarkers studies in UM. Outline of the workflow, which could lead to new biomarker discovery using a discovery proteomics approach.Results Conventional biomarkers described in other cancer types have been investigated in blood samples from UM patients. These markers have failed to provide reproducible results and therefore their usefulness in the clinical senario has been questioned. The enumeration of circulating tumour cells shows good potential, but results are influenced by the technique used for detection. Proteomic technology has been applied to UM tumour tissue, secretome and cell lines, mainly using 2D gels. Quantitative mass spectrometry‐based discovery proteomics comparing high risk tumours versus low risk ones, followed by system biology analysis to select a panel of meaningful candidates among the differential expressed proteins, bears the potential to be a more accuare and effective approach.Conclusion None of the blood biomarkers tested in UM patients have demonstrated the necessary sensitivity and specificity to guide clinical decisions. A rational development of clinically relevant blood biomarkers can be achieved applying proteomic technologies.
Staging of uveal melanoma metastases
Authors: KIVELÄ T , ESKELIN S 
Published: August 2012

AbstractPurpose To summarize the need and methods available to stage metastatic uveal melanoma.Methods Literature review and personal experience.Results In the Tumor, Node, Metastasis (TNM) classification, metastatic disease is assigned to category N1 (regional lymph node metastasis) and M1 (systemic metastasis) and stage IV by definition. For practical purposes, uveal melanoma spawns only systemic metastases. The latest 7th TNM edition, effective from January 2010, introduced subcategories of M1 based on the largest diameter of the largest metastasis (LDLM) at diagnosis of disseminated disease: M1a corresponds to LDLM 3.0 cm or less, M1b to LDLM 3.1‐8.0 cm and M1c to LDLM 8.1 mm or above. In addition to the TNM system, a staging system based on three variables: performance index as a measure of the general health of the patient, serum or plasma alkaline phosphatase level as a measure of the hepatic function and non‐measurable metastases and to LDLM as a measure of measurable metastases is available. It was developed at the Helsinki University Central Hospital and has been validated by the European Ophthalmic Oncology Group. An underlying multivariate model assigns patients into stages IVa, IVb and IVc with predicted median survival of less than 6 months, 6 to 12 months and over 12 months. In the validation data set, the corresponding observed median survival times were 18.6 months for stage IVa, 10.7 months for stage IVb, and 4.6 months for stage IVc.Conclusion Staging of cancer at diagnosis is important because it enables the physician to assess the extent of disease in a standardized way. This will help in choosing appropriate treatment and in assessing treatment outcomes between studies in a more comparable way.
Therapeutic options in metastatic uveal melanoma
Authors: PIPERNO‐NEUMANN S 
Published: August 2012

AbstractPurpose Despite the advances in the treatment of uveal melanoma (UM), randomized studies have demonstrated that the metastatic risk was similar after enucleation or conservative treatment. Survival has not improved and enucleation remains the treatment of choice for large tumors.Methods Up to 50% of patients develop metastases, to the liver in 90% of cases,usually leading to death. Metastases are rarely detected at the time of diagnosis, and in contrast with cutaneous melanoma, occur via hematogenous spread. There is no standard adjuvant treatment to prevent metastases. Today, genome‐wide techniques of genomic and expression profiling make it possible to improve the characterization of high‐risk UM. Recently, mutations in the GNAQ/11 genes have been described as oncogenic drivers in UM and consequently potential therapeutic targets. Since the identification of genomic abnormalities correlated with the metastatic risk, techniques of fine needle aspiration biopsies have been developed and systematic genetic analysis of UM became recommended for the next years, in the prospect of future adjuvant trials based on potential biological targets to be tested in preclinical animal models.Results Relevant clinical data and dedicated studies in metastatic UM patients are lacking. Only 25 prospective clinical trials were published in the last 30 years,none of them reported a randomized phase III trial. In a retrospective series of 470 metastatic patients managed at Institut Curie (2000‐2008), the median overall survival was 13 months, with a significant difference according to the first treatment in the metastatic setting: 28, 12 and 4 months for liver surgery, any systemic treatment, best supportive care respectivelyConclusion We will review current options and future developments for UM treatment.